Lightning rounds 38: Working in APP leadership, with Jason Wieland

We talk about working in critical care APP leadership positions, with Jason Wieland, PA, Lead Pulmonary & Critical Care APP at WakeMed Health System in Raleigh, NC.

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Episode 71: Transplant medications with Olivia Philippart

Photo by Tim Webb

We discuss the medications typically used after organ transplant, their impact on critical illness, and how to manage them when these patients show up sick—with Olivia Philippart, transplant clinical pharmacist specializing in liver and kidney transplant at University of Kentucky HealthCare.

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Takeaway lessons

  1. Most kidney transplants will end up on a calcineurin inhibitor like tacrolimus (or the older cyclosporine), an anti-proliferative like mycophenolate mofetil (Cellcept) or the older azathioprine, and possibly corticosteroids (e.g. prednisone). Formulations for some of these may need to be adjusted based on your formulary, so consult your pharmacist to get the equipotent dose.
  2. How these patients present, their degree of immunosuppression, and risk of rejection, are all heavily dependent on the time since transplant. A patient <6 weeks from transplant is high risk for nosocomial infections (e.g. post-op complications). A patient years out is mainly at risk of the same infections as anybody else, in addition to opportunistic infections related to their immunosuppression.
  3. Latent viral infections unmasked by immunosuppression or acquired from the transplant are usually not a surprise, as these are tested for as part of the initial workup.
  4. The highest risk of organ rejection and hence the highest degree of immunosuppression is in organs with substantial amounts of lymphoid tissue transplanted. The highest is small bowel, then lung, then heart/kidney/pancreas, then the least in liver (liver transplant can actually overall support immune function). Some livers can be maintained on monotherapy, while lungs usually need triple therapy, and often dual therapy is used in the middle category.
  5. Durations of therapy for identified infections may be longer in the immunosuppressed than for routine ICU care.
  6. Mycophenolate is the first agent to consider dose reducing or holding in the setting of active bacterial infection. How to handle this depends on the severity of infection and degree of concern for rejection.
  7. Both our calcineurin inhibitors (tacrolimus and cyclosporine) are primarily cleared in the liver and gut, so when there is liver impairment or bowel problems, dose decreases are often needed. Dietary intake also reduces drug absorption whereas NPO status may increase it. These drugs are heavily protein bound so albumin fluctuations (e.g. from malnutrition) may impact free levels.
  8. Drug interactions are common as well; CYP3A4 or PGP inhibitors like diltiazem or verapamil, azole antifungals, amiodarone, macrolides (although not azithromycin), and paxlovid will tend to increase levels, while inducers like phenytoin or phenobarbital will tend to decrease them.
  9. Overall, the therapeutic index of the calcineurin inhibitors is small, so have a low threshold for checking trough levels early and often.
  10. After holding a dose, the serum levels will normalize within 3-5 half-lifes, but full return of immune function may take several weeks. However, the baseline level of immunosuppression is usually not so profound that the difference between “off” and “on” is huge and binary.
  11. Organ rejection is possible but rare when drugs are acutely held (for days, maybe a week or two) in setting of severe infection, as this is already a relatively immunosuppressed state. However, this depends heavily on the time from transplant, and the organ transplanted.
  12. Mycophenolate levels (or mercaptopurine levels for the older azathioprine) tend not to fluctuate as much; the metabolism (via glucuronidation) is not as sensitive to hepatic function, so monitoring levels is rarely needed.
  13. Most of our immunosuppressants are not significantly renally cleared, so renal injury (even dialysis) usually require no dose adjustment. However, they can be nephrotoxic, so high levels may CAUSE renal injury, not vice versa.
  14. Tacrolimus is available in either immediate release capsule (taken twice daily) or a long-acting form (taken once daily). The latter helps to decrease peaks and some of the neurotoxicity (seizure, tremors), but cannot be opened. There is an 80% conversion between formulations (multiply the long-acting dose by 1.2, then divide by half to get the short-acting BID equivalent). Levels checked should always be troughs.
  15. Short-acting tacrolimus capsules should not be opened and put down tubes, but can be opened and given sublingually (50% dose reduction)—just dribbled under the tongue—although nurses need to take special precautions like gowning and double gloving. There is also a liquid tacrolimus formulation available.
  16. IV tacro exists, but has substantially higher nephrotoxicity, and the dose conversion is tricky; other routes are preferred.
  17. Cyclosporine is available in suspension which can go down a feeding tube, or via IV form (dose reduction needed).
  18. IV mycophenolate is available (1:1 conversion), as well as a liquid suspension.
  19. Steroids can be used in the ICU as usual (e.g. stress dosing), and indeed temporarily converting transplant patients to a pure steroid regimen is a reasonable approach during critical illness (remember: 20 mg hydrocortisone is equivalent to 5 mg prednisone).
  20. It’s generally sound to touch base with someone who knows a patient’s transplant history, even years out (often just their normal nephrologist, pulmonologist, etc in that case, not necessarily the original transplant team), when these patients are admitted for critical illness.
  21. Calcineurin inhibitors can cause headaches, seizures, even PRES, hyperkalemia and hypomagnesemia, and hypertension, hypercholesterolemia, hyperglycemia/diabetes. Attributing these effects to the drug is usually a diagnosis of exclusion.

References

From: Fishman JA. Infection in Organ Transplantation. Am J Transplant. 2017 Apr;17(4):856-879. doi: 10.1111/ajt.14208. Epub 2017 Mar 10. PMID: 28117944.

Lightning rounds 37: Weaning the deliriosedated patient (SCCM roundup)

A roundup of opinions from attendees at SCCM’s 2024 Critical Care Congress in Phoenix on strategies for rescuing the patient stuck in a loop of deep sedation and agitation.

Thanks to Pat Posa, Martha Roberts, Juliana Barr, Kelly Drumright, and Ben Lassow for their input.

Resources

  1. ICU Liberation.org
  2. ICU Delirium
  3. ICU Rehab Network

Episode 70: Airway evaluation for non-anesthesiologists, with Jed Wolpaw

We discuss assessing patients prior to intubation or other airway management, including both elective and emergent circumstances, with Dr. Jed Wolpaw, anesthesiologist and intensivist from Johns Hopkins, anesthesiology residency program director, and host of the ACCRAC podcast.

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Takeaway lessons

  1. Edentulous (toothless) patients are usually easier to intubate, but harder to mask ventilate. Heavy beards are harder to mask (can you trim it, or cover it with a Tegaderm?), larger neck circumferences, and larger tongues likewise.
  2. Consider the history, particularly involving the head and neck anatomy. Is there surgical history here? Jaw or oral surgery? Prior trachs or oral/neck radiation? Rheumatoid arthritis or Down syndrome (which can cause atlanto-occipital instability and may warrant trying to limit any forced neck extension)?
  3. Start by looking into the patient’s mouth (mouth open, sitting up, no “aah”):
    • Mallampati score (do you see the entire uvula, part of it, soft palate, or hard palate only?)
    • How is the dentition? Remove dentures if present. Are there loose teeth?
    • Is there an excess of soft tissue in the mouth (large tongue, etc)?
  4. Evaluate the thyromental distance (thyroid bump to chin); <3 cm (or fingerwidths) suggests a more “anterior” airway.
  5. Evaluate neck flexion and extension (passively if necessary) to appreciate limitations in neck mobility.
  6. If the patient is able, evaluate how well the jaw can protrude/prognath: ability to bite more of the upper lip with the lower teeth is a good thing. This is probably the single most predictive test for airway difficult, although it usually requires patient cooperation.
  7. Review the chart (or ask the patient) for prior documentation of intubation or anesthesia to determine if they have a history of a difficult airway. This can require some interpretation of the context and who was intubating previously. Good practice when documenting: write exactly what you did, and if it was difficult, write why! If you used a technique like awake intubation, a bougie, etc for elective or training reasons, document that reason so they don’t earn a label of a difficult airway forever.
  8. The STOP-BANG score is used to predict post-anesthesia airway obstruction (i.e. OSA), and probably has some association with faster deoxygenation and difficult mask ventilation, but is generally not super relevant for intubation.
  9. A patient with any concern for difficult intubation warrants consideration for factors also contributing to difficult LMA placement or cricothyrotomy. LMAs are difficult to place when the mouth opening is very small (about 2 inches) or the oral-laryngeal anatomy is unusual, and crics are difficult when the neck anatomy is impossible (eg a superimposed tumor, goiter, or heavily distorted anatomy). A patient who cannot have a cric may warrant an awake intubation to avoid the risk of inducing a patient who cannot be rescued.
  10. Obesity is not a predictor of anatomically difficult intubation. Mask ventilation may be a little harder if there is increased oropharyngeal soft tissue. It is a predictor of physiologic difficulty (faster desat), though.
  11. For emergent intubations: confirm code status, briefly evaluate the head/neck/mouth, use video laryngoscopy. Use hemodynamically stable agents for induction and reduce the dose, and ensure the team knows to subsequently sedate any patient who received a long-acting paralytic. Have a vasopressor drip ready, or better yet, running. Always set up everything and be prepared for every eventuality before you take away a patient’s ability to breathe.
  12. Either RSI with paralytics, or perform awake intubation. Otherwise, never RSI the critically ill without neuromuscular blockade, which will reliably reduce your chances of success. Short-acting paralytics (succinylcholine) are brief—i.e. not much longer than the apneic period of a short-acting sedative—and long-acting paralytics (eg rocuronium) can be reversed with suggamedex, in the rare situations where letting the patient wake up and resume breathing is a smart move.
  13. The one exception might be a ketamine-only intubation, which generally keeps the patient breathing, allowing you to either proceed to paralyzing or not depending on what you see, or maybe allow them to wake up.
  14. While it’s nice if an emergent intubation has been NPO, it probably won’t change your technique; changes in gut motility in the critically ill mean almost anybody can have stomach contents. Treat most ICU patients as if they have a full stomach, i.e. RSI. The one exception: the PREVENT trial showed that mask ventilation during induction (usually a no-no for RSI) of critically ill patients does not increase aspiration risk and does reduce hypoxemia, so should probably usually be done.
  15. In the highest aspiration risk patients like SBO or upper GI bleeding, keep the head of bed elevated, ensure ample/multiple suctions catheters, and be ready/willing to intubate the esophagus intentionally with your ETT and place it to suction to divert the stomach contents while you use a fresh ETT to intubate the glottis. Placing an NG beforehand to decompress the stomach is hit or miss as it can induce vomiting; it works better in a fully awake patient (who can manage any vomiting).
  16. We should probably still learn and teach direct laryngoscopy, but do so using a video scope with regular-geometry blade.

References

  1. PREVENT trial

Lightning rounds 36: Nurses are from Venus

Bedside nurses and providers (physicians, PAs, NPs) tend to see the world differently, much of it driven by their training and the systems they work within. We chat about reconciling this and how to best function as a team.