Note to myself: I’ve posted most of the content of Dr. Farkas’ great chapter separately for my ease of review. I review the first part of the chapter today:
The rest of the chapter I’m putting in separate chapters for my review and so I can find the topics more easily in my search function.
Note to readers: I only excerpt my study resources because doing so helps me fix the learning (sort of a like underlining in a textbook with a yellow highlighters-yeah, it probably didn’t work but I liked doing it). Readers should go directly to Dr. Farkas’ awesome chapter linked below.
Note to myself: Dr. Thomas who helps Dr. Farkas with the podcast recommends we review the entire written chapter before trying to listen to the podcast. For me, the best way to do this is to listen to the podcast as I review the chapter notes.
This chapter from Dr. Farkas has so much outstanding information that I have excerpted and post a number of sections separately (makes the subjects easier to find using my search function):
Here are direct links that Dr. Farkas has provided us to various sections of his chapter:
- Diagnosis & monitoring of pain
- Concept of multimodal analgesia
- Analgesic ladder for critically ill patients
- Other measures
- Questions & discussion
- PDF of this chapter (or create customized PDF)
Here are excerpts from the above chapter:
- Most ICU patients have some pain, particularly intubated patients. Inadequate pain control or overmedication are both problematic, so this requires thoughtful management.
- Opioids have traditionally been front-line analgesics in the ICU. However, these cause numerous side effects (delirium, constipation/ileus, vomiting, delayed extubation).
- For patients with ongoing pain, combining drugs from different pharmacologic classes may allow for effective analgesia while avoiding drug toxicity (multimodal analgesia).
- Whenever possible, the ideal approach is removal of the cause of pain (e.g., removal of unnecessary tubes/drains, management of constipation).
- This can be tricky in a patient with undifferentiated agitation: is the patient delirious, anxious, or in pain?
- Make sure that analgesics (especially opioids) are being used for pain control, and not as a blunt instrument to calm down agitated patients. Anxiety or delirium should be managed with an anxiolytic or antipsychotic – not an opioid.
- Patients able to communicate should be asked directly about pain.
- Among patients unable to communicate, behavioral pain scores may be used to assess pain (e.g., table below). This isn’t perfect, but it provides a systematic approach to assess pain and titrate medication accordingly.
Multi-modal therapy is a useful principle which may be applied to a variety of topics (e.g., sedation, hemodynamic support, antiemetics).
- Increasing medication dosing increases both therapeutic and toxic effects, as shown above.
- Using lower medication doses can often allow substantial clinical benefit, with minimal toxicity (optimizing the risk/benefit ratio). This also creates a safety buffer; even if drug concentrations increase a bit, they will remain within a safe range.
foundational concept #2 = different agents function synergistically
- Different analgesics frequently work in a synergistic fashion (i.e., 1+1 = 3).
- Synergy allows moderate doses of several different agents to have a large combined impact.
putting it together: multi-modal therapy
- A multi-modal strategy therefore involves using moderate doses of several different agents, in order to maximize efficacy while minimizing toxicity. This is in contrast, for example, to a traditional approach of drowning patients with super-human doses of a single opioid (a strategy which is effective, albeit at the cost of considerable toxicity).
- Multi-modal therapy is more work, because it involves administration of more medications. This may be confusing to practitioners who aren’t familiar with it (“why are we using four drugs when we could use one?”). However, the evidentiary basis for multi-modal therapy is reasonably robust (based largely on RCTs performed in operative and post-operative patients).
analgesic ladder for critically ill patients
The concept of an analgesic ladder was developed by the World Health Organization in 1986, as a theoretical construct to encourage rational use of opioids. It focused on optimizing the use of non-opioid analgesics, before escalating to opioids. This may be adapted for critically ill patients a shown here:
There is no one-size-fits-all solution to analgesia among critically ill patients. For example, patients with neuropathic pain may benefit from up-front initiation of a gabapentinoid, whereas most other patients probably won’t. That said, the above schema may provide a rough guide to when different types of medications may be initiated. In particular, the typical progression from PRN opioids straight to an opioid infusion should be avoided.
Note to myself: I’ve posted the rest of my review of Dr. Farkas’ chapter Analgesia For The Critically Ill Patient [Link is to the complete chapter] from the Internet Book of Critical Care [Link is to the Table Of Contents] in separate posts to help remember all the great pearls.
general comments & mechanism of action
- Acetaminophen is a mild-moderately effective analgesic with an excellent safety profile. It forms the first level of the analgesic ladder due to its safety, rather than its efficacy. Acetaminophen is often overlooked because it isn’t very potent. However, scheduled acetaminophen may nonetheless play a useful role in multi-modal analgesia. RCTs and meta-analyses demonstrate that acetaminophen is an effective analgesic in a variety of contexts, with benefits which may include reduced opioid requirements, avoidance of delirium, and avoidance of nausea/vomiting. (20189753, 30726545, 30305124, 30778597)
- Acetaminophen is a centrally acting, noncompetitive reversible inhibitor of cyclooxygenase (COX) enzymes, with analgesic and antipyretic effects. (30845871)
- The usual dose is 650-1,000 mg q6hr. For patients with ongoing pain this should be scheduled, to provide a baseline level of analgesia.
- Acetaminophen may be given PO, PR, or IV. PO is preferred, because IV is expensive (although this varies in different countries).
- Available RCTs have found no difference in efficacy between IV versus oral route.
- 📚 Medscape monograph on acetaminophen
contraindications & complications
- In severe alcoholism, stable cirrhosis, or low body weight (<50 kg), the dose should be reduced to 2 grams per day (at most).(25477978)
- In acute liver injury* or decompensated cirrhosis**, acetaminophen should be entirely avoided.
- In neutropenia, acetaminophen might be avoided, to allow for early detection of neutropenic fever.
*Please see Acute Liver Failure – LiverTox – NCBI Bookshelf, Dec 11, 2019
**For an explanation of the diagnosis of compensated cirrhosis versus decompensated cirrhosis, please see Stages of Cirrhosis from Viral Hepatitis and Liver Disease from the U.S. Department of Veterans Affairs. Accessed 2-23-2021.
general comments & mechanism of action
- Ketamine functions as an NMDA inhibitor. At very low doses, ketamine provides analgesia without other neurologic effects.
- Pain-dose ketamine infusions provide a mild to moderate level of analgesia (with some variation between patients). This often isn’t sufficient to control the pain entirely, but it may provide a continuous basal level of analgesia with opioid-sparing effects. (25530168)
- Increasing evidence supports the use of pain-dose ketamine infusions among critically ill patients. (12933413, 26025196, 28468568)
- Pain-dose ketamine infusions are extraordinarily safe, especially in an ICU environment (noting that low-dose ketamine infusions can be given safely on the wards). Of all the medications described in this chapter, ketamine is arguably the safest one.
- Ketamine doesn’t suppress respiration or airway protection.
- Ketamine doesn’t cause hypotension (occasionally ketamine may increase the blood pressure, but generally not substantially).
- The main limitation of pain-dose ketamine infusions is that they’re a bit of a hassle to set up (compared, for example, to opioid boluses, which are faster to give and more immediately gratifying).
benefits of a pain-dose ketamine infusion
- (1) Mild-moderate analgesic effect, reducing the required dose of opioids.
- (2) Ketamine may inhibit the development of tolerance to opioids and the emergence of opioid induced hyperalgesia. (15983467, 16854557, 23269131, 14581110) Thus, ketamine may mitigate some side effects of opioids.
- (3) Ketamine exerts antidepressant effects, which may improve patient mood and promote participation in rehabilitation. (26025196, 23428794, 16894061)
risks of pain-dose ketamine infusion: psychomimetic side effects
- The only true risk of pain-dose ketamine infusion is psychomimetic side effects. At the higher dosing end (around 0.2-0.3 mg/kg/hr), ketamine may cause somnolence, agitation, euphoria, or hallucinations. Often these effects may be beneficial (e.g., mild sedation or euphoria). However, some patients may experience disturbing hallucinations.
- Psychomimetic side effects will abate rapidly after pausing the ketamine infusion, so this isn’t a major problem if managed appropriately.
- One randomized controlled trial found that pain-dose ketamine infusions reduced the risk of delirium. (30268528). This suggests that the possibility of psychomimetic side effects doesn’t imply a danger of more serious neurologic complications from ketamine.
nuts & bolts of pain-dose ketamine infusions
- The typical dosing range is 0.1-0.3 mg/kg ketamine per hour (e.g., ~8-20 mg/hour).
- If you’re extremely worried about psychomimetic side effects, you could just leave the infusion at a fixed rate of 0.12 mg/kg/hour. Several studies suggest that the risk of psychomimetic effects at that dose is close to zero. (25530168, 15983467, 21676160) This strategy might be reasonable in an intubated patient with baseline agitation, where it may be difficult to determine whether the patient is experiencing psychomimetic side effects.
- For most patients, it’s useful to start at the lower end of this dosing range, and then uptitrate the ketamine gradually over a period of hours as needed. If troublesome psychomimetic side effects occur, then pause the ketamine infusion for an hour or two and resume at a lower dose (a dose which didn’t cause psychomimetic side effects).
- Psychomimetic side effects are dose related, and therefore not a contraindication to using ketamine.
- Resuming ketamine at a lower dose can often still allow the patient to receive substantial benefit from ketamine, without experiencing any side effects.
- The combination of ketamine with a central alpha-2 acting sedative (dexmedetomidine or clonidine) or with propofol appears to prevent the occurrence of psychomimetic side effects.(15235947) This may allow higher doses of ketamine to be given (e.g., doses up to ~0.5 mg/kg/hr). More on this below.