CONTENTS
- Introduction
- Basic principles of medication reconciliation
- Specific medications:
- Questions & discussion
When a patient is admitted to the ICU, which of their outpatient medications should be continued? This is a rather mundane task, one which is often delegated to junior team members. However, these decisions can be quite important.
It's not possible to provide a complete guide on how to manage every medication in every patient. The goal of this chapter will be to provide a general framework for doing this, as well as a discussion of some considerations regarding common medications.
(#1) Figure out what the patient is actually taking at home
- Electronic medication lists often don't correspond with reality.
- PRN medications (e.g., PRN lorazepam) – are they taking it regularly, or occasionally?
- The best source is often the patient or the family.
- Other sources: collateral information from pharmacy (are they filling prescriptions?).
- Patients transferred from a facility will have an accurate medication administration record – make sure to get it.
(#2) Figure out WHY patients are on various medications
- Ideally, all prescriptions would have indications attached to them. Unfortunately, they don't.
- Indications matter; for example, a patient could be taking aspirin for numerous possible indications, including:
- (1) No good reason (primary prevention)
- (2) Coronary stents.
- (3) AERD (aspirin-exacerbated respiratory disease), discussed here.
- Indication will drive the dose and importance of continuing aspirin (more on this below).
(#3) Consider renal and/or hepatic failure
- ICU patients often have organ failures, especially renal failure.
- Any home medications that are continued must be re-dosed based on organ failures.
(#4) Avoid nephrotoxic & deliriogenic medications as able
- ICU patients are at high risk of renal failure and delirium.
- Common nephrotoxins to hold: NSAIDs, ACEi, ARB.
- Common deliriogenic medications to hold: PRN benzodiazepines (if not using frequently).
(#5) When in doubt, err on the side of holding medications
- Patients are often on numerous medications, many of which are unnecessary during their hospital stay (e.g., medications directed towards management of chronic problems). It's generally beneficial to discontinue extraneous medications for the following reasons:
- Avoids interactions with new medications started in ICU.
- Reduces unnecessary burdens on nursing & pharmacy care.
- Focuses attention on more important medications.
- Simplifies management overall (e.g., if there is a potential adverse drug reaction, being on fewer medications may clarify which medication is causative).
- (Further discussion behind the rationale for holding extraneous medications is here.)
(#6) We should probably run the final medication list through an interaction checker program
- Ideally, this would be built into the hospital's electronic medical record system. Unfortunately, many electronic medical records are unable to comprehensively detect and display interactions between medications that the patient is receiving.
- MedScape and Epocrates are more thorough. However, these programs may be overly sensitive, leading to the detection of an excessive number of interactions.
- MedScape drug interaction checker is here.
- Using an interaction checker program is especially important for patients on uncommonly utilized drugs that are subject to numerous drug-drug interactions:
- Transplant medications.
- HIV medications.
- Cystic fibrosis transmembrane modulators.
beta-blockers
- The indication for the beta-blocker is an important determinant of how important it is:
- Beta-blockers for rate control of atrial fibrillation or heart failure management are more important to continue.
- Beta-blockers initiated solely as management for chronic hypertension are less important to continue.
- Beta-blocker discontinuation theoretically may cause a surge in sympathetic tone, causing an increased risk of myocardial infarction.
- Beta-blockers may impair perfusion for patients in shock. They may also block the heart's ability to respond to hemodynamic challenges (e.g., this could be dangerous in a patient with submassive pulmonary embolism and threatened massive PE).
- Beta-blockers are generally contraindicated in patients with shock or bradycardia.
- Ultimately this is determined on a patient-by-patient basis, depending on hemodynamics and predicted clinical trajectory.
diltiazem
- This is most often used for management of atrial fibrillation.
- In hemodynamically robust patients, diltiazem should usually be continued to prevent AF with rapid ventricular response.
- When in doubt, hold diltiazem and follow the hemodynamics.
ACE-inhibitors / Angiotensin-receptor blockers (ARBs)
- These impair the ability of the kidney to adapt to hypoperfusion, thereby increasing the risk of acute kidney injury in response to hypoperfusion.
- ACEi and ARBs should generally be held upon ICU admission.
- Exceptions where continuing the ACE inhibitor makes sense:
- (a) Anuric patients on chronic dialysis, who are not at risk for worsening renal function.
- (b) Hemodynamically stable patients with severe heart failure, in whom the ACEi is being used to treat heart failure.
most other antihypertensives
- Continuation is based on a judgement of the severity of hypertension versus risk of hypotension. When in doubt, it's generally better to hold long-acting antihypertensives (err on the side of a slightly higher Bp). It's somewhat easier (and perhaps safer) to allow the Bp to drift a little high and then treat with PRN antihypertensives (rather than inducing hypotension that requires a vasopressor).
- Dihydropyridine calcium channel blockers (e.g., amlodipine, nifedipine extended release) can often be continued. These are among the more benign antihypertensives.
- Clonidine should not generally be discontinued if possible (discontinuation may cause withdrawal hypertension).
digoxin
- Hold further doses & check a digoxin level.
- Subsequently, consider resuming digoxin with daily monitoring of levels.
statins
- Discontinue statins in patients who are on other drugs that may cause myopathy (e.g., daptomycin).
diuretic
- These may be held initially if the patient is hemodynamically unstable.
- It's generally reasonable to add back home diuretics as soon as possible. If this is forgotten, it will promote volume overload.
- Some patients won't produce much urine without diuretics – be conscious of this and don't chase their low urine output with fluid.
inhalers for COPD/asthma
- Acutely ill patients are usually too sick to take medications via a metered-dose inhaler or dry power inhaler (this requires a fair amount of coordination and effort).
- It's generally best to hold all chronic inhalers at the time of admission to the ICU.
- Patients without acute lung disease can often be treated with PRN albuterol nebulization.
- Patients with an acute exacerbation of COPD can be treated with albuterol/ipratropium nebulization q4-q6hrs plus PRN albuterol.
proton pump inhibitors
- These are generally continued (new evidence with SUP-ICU suggests that proton pump inhibitors don't actually increase the risk of C. difficile)
antiplatelet agents (e.g., aspirin, clopidogrel)
- Key factors to consider:
- (1) What is the strength of indication (e.g., status post coronary stent is a strong indication, versus primary prevention's being a weak indication).
- (2) Net state of anticoagulation and risk of DVT (aspirin has weak activity in preventing DVT, so it could be beneficial in patients at high risk for DVT who are at low risk of bleeding).
- For patients on aspirin for no specific indication (“primary prevention”), this should generally be stopped. Especially among intubated patients, unnecessary aspirin may promote stress ulceration.
- When in doubt, these can often be held for 24 hours to sort things out (these agents take several days to wear off anyway).
warfarin
- Check a baseline INR.
- The decision to continue warfarin depends on bleeding risk, requirement for procedures, strength of indication for warfarin, and INR level.
- For patients on warfarin with acute hemorrhage, immediate reversal may be beneficial: 📖
- For patients with supratherapeutic INR who aren't actively bleeding, a more conservative strategy for vitamin K administration may be utilized: 📖
DOACs (direct oral anticoagulants)
- DOACs are VERY problematic among patients who are critically ill, due to a relative inability to reverse them. This is hugely problematic if:
- (a) There is spontaneous hemorrhage.
- (b) Procedures need to be done (especially neuraxial procedures such as lumbar puncture).
- 🚨 DOACs are renally cleared, so patients with acute kidney injury on DOACs will often present with supra-therapeutic drug levels. These patients may remain functionally anticoagulated for days (even without any additional DOAC administration).
- General approach to DOACs:
- Hold them.
- Check an anti-Xa level.
- Further management depends on anti-Xa level, strength of indication for anticoagulation, and renal function. If anticoagulation is needed, then heparin may be started at some point (either heparin infusion or low molecular-weight heparin). Note that DOACs may render a patient anticoagulated for days in the context of renal failure.
erythropoietin
- Erythropoietin hasn't been shown to be beneficial in ICU.
- Generally this is held for patients with active critical illness.
non-insulin diabetes medications
- Hold all of these (especially metformin).
- Glycemic control in the ICU should be managed with insulin.
basal (long-acting) insulin
- In Type-I diabetes, this MUST be continued without any dose reduction. Hypoglycemia should be anticipated and managed with the administration of carbohydrate (e.g., tube feeding or IV dextrose).
- In Type-II diabetes:
- For shocked patients who are severely unstable: discontinue this and use IV insulin as needed (absorption of sq insulin may be erratic).
- For most patients, long-acting insulin should generally be continued. Systemic inflammation and steroid utilization increase insulin resistance, so patients may tend to experience hyperglycemia in the ICU. If there is concern regarding hypoglycemia, a 50% dose reduction may be reasonable. Follow glucose levels and titrate appropriately.
steroid
- Chronic steroid should generally be continued. Patients on chronic steroid will be adrenally insufficient (to an extent proportional to the dose and duration of their steroid therapy). Dose escalation may be considered in patients under considerable stress:
- For patients with shock it's generally wise to transition to a full stress-dose of steroid (e.g., 50 mg IV hydrocortisone q6hr).
- For patients who are under stress but not shocked, a moderate increase in steroid dose may be reasonable (e.g., increasing from 10 mg prednisone daily to 20 mg prednisone daily).
thyroid replacement (levothyroxine)
- This should be continued.
- Levothyroxine has a long half-life, so if the patient misses a few doses it's OK.
- For patients who will be unable to take enteral medications for several days, intravenous levothyroxine may be utilized.
antiepileptic agents
- These should nearly always be continued.
- They may require conversion to intravenous administration (note that levetiracetam has 1:1 conversion).
antidepressants (e.g., SSRIs and SNRIs)
- These should generally be continued.
- Discontinuation syndrome is possible, especially with SNRIs (e.g., venlafaxine).
- Exception: For patients who are deeply sedated with an anticipated prolonged duration of mechanical ventilation, discontinuation of SSRIs/SNRIs may be wise in order to reduce the risk of iatrogenic serotonin syndrome (since patients may often receive several serotonergic medications such as fentanyl, ondansetron, and olanzapine).
chronic opioids
- Chronic opioids generally cannot be stopped in the ICU (due to the potential for withdrawal).
- For patients with tenuous mental status or hypercapnia, opioid doses may need to be scaled back (yet not stopped entirely).
- For patients with acute pain, consider the addition of non-opioid analgesics (e.g., ketamine infusion, acetaminophen) – rather than ramping up the opioid dose. (Further discussion of multimodal analgesia here: 📖)
chronic buprenorphine for management of opioid use disorder
- (1) If at all possible, buprenorphine should be continued. (Sublingual buprenorphine may be given to intubated patients, although this isn't necessarily ideal.)
- (2) Strategies for management of acute pain include:
- (a) Dividing the buprenorphine dose q8hr.
- (b) Increase in buprenorphine dose.
- (c) Non-opioid medications (e.g., acetaminophen, ketamine).
- (3) Avoid full opioid agonists if possible. Consider working with anesthesia/pain services to manage complex pain issues that may arise in these patients.
- (4) Patient MUST be discharged on buprenorphine.
- (There is a whole section on this in the chapter on opioid use disorder here.)
antipsychotics
- These should generally be continued if possible (although if the patient is obtunded, antipsychotics may need to be held or dose-reduced).
- Clozapine should be continued if at all possible (if discontinued, then clozapine must be resumed with a gradual dose up-titration).
Parkinson medications
- Rapid withdrawal of medications for Parkinson disease may precipitate severe symptoms (including neuroleptic malignant syndrome).
- Ask the patient/family what happens if the patient misses their medications. This may help evaluate the risks involved in medication discontinuation.
- In the context of severe Parkinson disease, these medications need to be continued.
- When in doubt, work with pharmacy and/or neurology consultants.
- (Whole section about Parkinson medications here.)
baclofen & gabapentin
- These share some fundamental similarities:
- They are cleared by the kidneys. In renal failure, they will accumulate and potentially lead to obtundation (especially baclofen).
- Complete discontinuation may lead to withdrawal.
- In general:
- For patients who are obtunded, hold these temporarily. Subsequently, once the patient is awake, resume therapy at half the baseline dose with up-titration over time.
- For patients with intact mental status, continue therapy (with renal dose adjustment as appropriate).
deliriogenic medications
- These includes the following agents:
- Benzodiazepines.
- Antihistamines (e.g., diphenhydramine).
- Zolpidem.
- Muscle relaxants (e.g., cyclobenzaprine).
- In general, these drugs cause delirium in the ICU and should ideally be avoided.
- However, for patients who take these chronically (e.g., for sleep) it may be best to continue them. This is especially true of benzodiazepines (discontinuation may cause withdrawal, seizures, and even catatonia).
- Continuation and correct dosing of transplantation medications is EXTREMELY IMPORTANT.
- Patients generally are associated with a transplant center – discuss medication dosing with the patient's transplant physicians:
- Information to gather prior to calling the transplant center is discussed here.
- Information to get from the transplant center:
- Recommended doses?
- What are their target drug levels? (e.g., tacrolimus level).
- It's generally wise to consult with a local transplant physician if there is any doubt about medication dosing (especially if unable to reach the patient's outpatient transplantation physicians).
- Whenever starting ANY drug in these patients, look for drug-drug interactions with their immunosuppressive regimen using a pharmacopeia tool (e.g., MedScape or Epocrates).
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