Critical Care Scenarios – Educational critical care scenarios presented in a podcast format.

Episode 100: Autoimmune encephalitis testing with Tammy Smith

Tammy Smith, assistant professor of neurology at the University of Utah within the division of Neuroimmunology and Autoimmune Neurology, and a clinical consultant at ARUP Laboratories, gives us the inside scoop on testing for autoimmune encephalitis syndromes.

Learn more at the Intensive Care Academy!

CHEST’s Procedural Skills for the Critical Care Clinician, April 23-24 2026

Takeaway pearls

When should you suspect autoimmune encephalitis in the ICU?
- Subacute symptoms (1 week to a couple months) of behavior changes, episodes of confusion, speech, wakefulness (sleeping too much or not at all).
- MRI with changes consistent with encephalitis
- Intractable seizures not easily controlled with ASMs
- History of malignancy
Antibody assays for autoimmune encephalitis are available from the Mayo Clinic, ARUP labs, as well as Quest, Athena, and Labcorp. As a rule, they go to such reference labs and are not performed in-house. Some allow individual antibody tests, while many only perform them as a panel. The turnaround time for these tests is often about two weeks. They usually use either tissue- or cell-based assays.
Most of the antibodies originally identified as causing autoimmune syndromes were paraneoplastic in origin, i.e. directly linked with malignancy. Now we are identifying an increasing number that have only a general association with malignancy (eg anti-NMDAR encephalitis), or none at all.
These panels are often some of the most expensive tests you can send; try to send them thoughtfully. ~95% of these panels (in Mayo’s published data and internal ARUP data) are completely negative, and while some of those are probably “misses” (eg the patient has an as-yet unknown antibody), many were probably unnecessary. Also problematic is incidental positives, usually irrelevant antibodies at low titers, which may then lead to needless worry and clinical confusion.
The Graus criteria provide some guidance for apparent antibody-negative encephalitis syndromes. In general, with negative tests, clinical or imaging progression despite your empiric therapy should raise the question of another missed diagnosis (eg a genetic disorder), while clinical improvement may make you think you had the right diagnosis but the test missed it.
The timeline for response to therapy varies. Pulse-dose steroids come on pretty fast (within days), and dissipates within a few days. IVIG lingers in the body around a month, and a full course of PLEX has an impact for about that long as well (about 80% antibody recovery in 1 month). PLEX is also removing other inflammatory molecules contributing to the syndrome. It’s usually best to wait about a week on one therapy before considering adding a second line (though the EXTINGUISH trial is trialing earlier introduction of immunotherapy for anti-NMDAR).
Some tests may report qualitatively (negative/positive), usually due to technical issues, but most will try to report a titer. In general higher titers are more likely to be relevant, or at least more demanding of a clinical explanation, although exact cutoffs are usually not defined. Titer does not correlate well with disease severity, however.
In general, send both a serum and CSF panel. The CSF may be more specific (antibodies in the CSF are more likely to be clinically relevant), while the serum is often more sensitive (as the antibodies are usually created here).
Prior treatment affects testing in this way:
- Steroids: probably not much
- PLEX: will transiently clear the antibodies, reducing sensitivity of your tests. (Make a note in the chart so people know a negative late test may have been falsely negative.)
- IVIG: probably does not reduce sensitivity much, but may increase the false positive rate a little, as a tested antibody could be present within the pooled IVIG), especially common antibodies like GAD-65.
ARUP has a matrix to help guide selection of the right panel. Most of the reference labs have somewhat phenotyped panels, eg one for encephalitis, one for encephalopathy, one for movement disorders. However, when the patient has overlapping symptoms, you usually do not need to send multiple panels, as they may test many of the same antibodies. Check what’s being tested. Most also offer a “everything” panel if you’re not sure what you’re doing, but it increases your risk of incidental positives.
ARUP does have a hotline offering 24/7 expert assistance if you’re not sure what you’re doing.
New antibodies are regularly added to these panels, although they’re not always completely current, so a local expert who may be aware of newer evidence of an emerging antibody not part of your panel can sometimes suggest sending something extra.
While many antibodies are still undiscovered, it is probably true that the most common and important ones have been found at this point.
In most suspected autoimmune encephalitis syndromes, especially with an antibody associated with malignancy, it is appropriate to do a broad screen for an underlying neoplasm. A contrasted pan-CT at least is reasonable. Though in fairness, the true paraneoplastic syndromes (>70-90% association with cancer) such as anti-Yo are also among the most rare encephalitis syndromes. With the highest risk antibodies, even pursuing a PET scan makes sense.
With anti-NMDAR, ultrasound of the ovaries and perhaps testicles is appropriate due to the incidence of teratomas. Any abnormality on the ovaries should be considered suspicious, even if it has a generally benign or cystic appearance; some of these are microscopic tumors. In a refractory patient, empiric oophorectomy/orchiectomy can even be considered after shared decision-making.
Other than anti-NMDAR, the most common antibodies are LGI1, GAD65, and CASPR2. In general though, it is probably unreasonable for non-subspecialists to guess a specific antibody; suspect the broad disease.
A good reason to seek subspecialty consultation or transfer would be: severe autonomic instability, lack of comfort with or access to treatment (eg rituximab, PLEX, etc), or failure to respond to initial therapies. One common issue is for community hospitals to report they’ve “sent the tests,” when in fact they’ve sent a panel that doesn’t include some important antibodies. Find out exactly which tests were done (for example, the Mayo and ARUP “paraneoplastic” panels do not include NMDAR, as it is not technically a paraneoplastic syndrome, even though it has an association with neoplasm).

Lightning rounds 64: The new Surviving Sepsis guidelines with Hallie Prescott

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Hallie Prescott, pulm/crit physician and co-chair of the recent Surviving Sepsis guideline writing committee, gives some insight into the new document, including a few interesting additions and some points of controversy.

For more thoughts, especially from an EM perspective, Scott Weingart also interviewed Hallie over at EMcrit.

Learn more at the Intensive Care Academy!

Takeaway pearls

The new guidelines suggest/recommend:
- Prehospital sepsis screening, and in systems with >60 minutes to hospital evaluation and the appropriate systems in place, prehospital antibiotic administration. (This is a fairly narrow recommendation that won’t apply to many in the US, mostly rural systems with long transport times.)
- Don’t give anaerobic antibiotic coverage if not suspicious of anaerobic infection
- Target a MAP >65 in most, but in patients >65 years old, target only >60.
- Don’t use qSOFA exclusively for screening; use other more sensitive tools like NEWS.
- Consider SDD (selective decontamination of the digestive tract), the use of targeted local and systemic antibiotics in intubated patients to reduce the bacterial load in the upper GI tract and reduce the risk of VAP. This has a long presence in the literature and is more practiced in Europe than the US, but the data is fairly good.
- Suggest measuring serum lactate, and perhaps trending it, but not necessarily trying to normalize it.
- Prolonged infusions of beta-lactam antibiotics are supported (for subsequent doses; the first dose should still be a bolus) due to reasonably positive data.
- If final cultures are negative, consider deescalating/stopping antimicrobials. (Obviously, this means most patients have already received a few days of therapy by then.)
Other old standards like 30 cc/kg fluid boluses and early antibiotic administration remain. Some are upset about this, as they have been translated into US quality measures (the SEP-1 CMS standard) that invoke monetary penalties when not adhered to—a standard that has caused much headache for EM particularly. But Hallie says: this is a global standard with >25 nations involved, and is oriented around medical realities. Translating it into national quality standards, rightly/wrongly, appropriately or bluntly, is not the business of the guideline group, and is purely an American issue.

Lightning rounds 63: How to be right, with Scott Weingart

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Scott Weingart, ED intensivist and seminal educator from the EMCrit podcast, shares his thoughts on how we should be finding truth nowadays: how to read journals, choose experts, use AI, and resolve disagreement.

Learn more at the Intensive Care Academy!

Takeaway pearls

Scott subscribes to around 60 journals and reads them monthly, meaning skimming the topic index, then for any titles that jump out at him he reads the abstracts, then the actual article for any that still look relevant. He doesn’t recommend doing that. Reading around 10 journals would get you most of the high-yield updates, and you could probably get away with 3–4. It’ll take you about an hour a month.
Read at least the methods and results. The discussion, abstract, and conclusion are mostly a mini-review paper. Ask: is this “generalizable,” meaning applicable to me—my patients, my practice, my questions? Could we implement this here? Ask also how your personal clinical expertise bears upon this (sometimes it’s greater than that of the authors). Finally, ask if the rigor of the paper supports the findings, though you may need to turn to methodological experts here given the complexity of modern studies. (Statistical and methodological experts are available out there, whether in your department or on the internet.)
Signals of confidence, charisma, or “reasonableness” are no longer useful (if they ever were) markers of good knowledge in experts, authorities, pundits, authors, podcasters, etc. In fact, truth-tellers are often less compelling communicators, as they tend to hedge and equivocate; that’s what the truth looks like, not clear messages, the latter of which are often fabricated.
One tool for managing this: seek disconfirmation. When pursuing opinions and expert perspectives, don’t look for those that agree with your prior beliefs, look for those that disagree; that is far more likely to be meaningful and useful data if you’re truly curious about what you’ll find. Even if your mind isn’t changed afterwards, your beliefs will become clearer and deeper. Especially in the current era of algorithms, subcultures, echo chambers, and AI tools that tend to agree with you, you need to actively seek these differing views. You should be able to make the counter-argument to your beliefs better than anyone who truly believes it—that’s when you really understand your own views.
When you find a differing view, rather than engaging knee-jerk opposition, ask why? What is different in their population, approach, environment, etc that leads to a differing view from this reasonable person? If your first reaction is “WTF are you talking about?” try to transition into “Hmm… wtf are you talking about?”
Clinical experience always needs to be thoughtfully integrated into the literature. The subtle lessons of experience are not always studied, and a large study of pooled patients may not address this specific patient’s situation. However, we also tend to overweigh the value of personal lessons, especially when it comes attached to emotional experiences.
A psychological pitfall for educators, and especially modern content creators (podcasters, bloggers, talking heads, YouTubers, etc) is the pull of speaking to create controversy rather than truth. We have lost great scientists and clinicians from the realm of real medicine towards hucksterism by this temptation.
AI today is reasonably good at acting as a medical librarian, i.e. “tell me (with references) the major studies addressing this point.” For this purpose, it is probably better than limited attempts at scouring the literature with PubMed, although all it’s doing is scouring the Internet for commentaries that have referred to the literature, and may therefore miss smaller/less known studies. It is less good at answering specific clinical questions, although it can be a useful idea generator, such as suggesting possibilities for your differential you hadn’t considered… since it remembers all facts, and is good at pattern recognition.
Fight the natural tendency of AI agents to be agreeable by prompting them towards disconfirmation, i.e. “tell me where I’m wrong.” If you solicit agreement or even use a neutral framing, they will tend to roll with whatever you suggest.
When thinking or teaching, you will be more right and righteous if you speak in probabilities or allow the possibility of uncertainty, then if you speak in platitudes. Say you could be wrong, estimate a degree of probability… if you think in certainty, you anchor yourself and can never become more correct with new data.
95% of your decisions should be made in advance, either as shared or internal guidelines, based on your current assessment of our knowledge and how you do what you do. The other 5% will require intensive thought at the time, which is a good thing as long as it’s only 5%, and maybe you can generalize your decisions so that decision will be autopilot next time.
Listen to differing perspectives and opinions from different sources to add qualitatively to your market of ideas, without trying too hard to weigh which is a “better” opinion or source, as this is mostly impossible; with that perspective, you don’t need to worry as much about the validity of the source as long as it’s worth hearing.
However, give very little weight to “voting,” or considering how often you hear a perspective. In the modern era of algorithmically served content, media echo chambers, and self-selecting subcultures, as well as the growing rise of completely AI-generated content in infinite volumes, you are likely to hear many voices that share the same opinion, regardless of whether it’s right or wrong, and quantity of perceived voices may have no correlation to the actual number of people who believe something. In fact, many seemingly different sources are really just echoing or referring back to one original source, not reflecting new opinions. “I hear it all the time/everyone thinks that” is no longer a useful tool for finding truth.

Episode 99: RV failure in the MICU

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We chat about managing a complex MICU patient with RV failure in the setting of renal failure and sepsis, with Amos Dodi, nocturnal intensivist at Einstein/Montefiore and author of a recent narrative review on the RV.

Learn more at the Intensive Care Academy!

CHEST’s Procedural Skills for the Critical Care Clinician, April 23-24 2026

References

Amos’s RV failure review: Dodi, A.E., Jacobs, M. Acute Right Ventricular Failure in the Medical ICU. Lung 203, 107 (2025). https://doi.org/10.1007/s00408-025-00862-y

Takeaway pearls

Distinguishing the cause of shock in a patient with chronic PH is always challenging. Echo can be harder to interpret, but extremes can be called: frank hypovolemia, frank RV failure. Don’t forget to correlate clinically, eg feeling the extremities to estimate SVR.
Measuring CVP can be very valuable in these patients. The spot value can be hard to interpret, but trends can be revealing; if the CVP suddenly jumps, consider the RV is giving up.
Response to therapy can also be a potent diagnostic tool, such as the response to inotropy, or a fluid challenge.
Avoid hypoxemia, hypercarbia, hypotension, acidosis, all of which increase the PVR and hence RV strain. Limit fluid inputs from drips.
Favor vasopressin as a PVR-sparing pressor, perhaps with low-dose epinephrine as a titratable inopressor, though caution with vaso causing coronary ischemia in an RV already at risk of it due to dilation.
Intubating the RV failure patient should be done with great caution and respect, and really, deferred if possible. The team should proceed with awareness of the risk of hemodynamic decompensation (ideally one provider tasked to this purpose peri-intubation). Induction agents should be hemodynamically stable, preoxygenation should be optimal, and be delicate with BVM use to limit intrathoracic pressure.
A PA catheter has potential utility, although expertise has dwindled these days. It is not impossible that placing a foreign body across the TV, through the RV into the PAs could even worsen RV function somewhat. Non-invasive cardiac output monitors may have a role as well although the benefit has not be clearly shown.
Volume management and diuresis can sometimes be guided by the urine sodium.

Lightning rounds 61: Credentialing and privileging, with Christopher Newman

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We dive into the confusing rabbit hole of medical staffing, credentialing, and privileging, particularly for the critical care APP, with Chris Newman, pediatric critical care PA and Vice Chair for Clinical Performance at the University of Colorado.

Check out the REVIVE conference here!

Check out the CHEST Procedural Skills for the Critical Care Clinician course here!

Learn more at the Intensive Care Academy!

Takeaway pearls

The medical staff office regulates the medical staff, which includes physicians and APPs. The latter may actually be voiting “members” of the medical stuff, or have some kind of affiliate status; the relevance of this is their eligibility to vote and sit on its committees, which sets the policies and manages governance. Either way though, APPs are subject to the medical staff office’s regulation.
Credentialing is the process of ensuring medical staff have the right and competence to work in the hospital, mostly confirming basic job requirements like graduating training programs. Privileging is the process of determining what specific things you are allowed to do in the hospital.
Privileges are broken into core privileges, which are things any provider should know how to do (i.e. taught in school): perform H&Ps, order meds and tests, interpret them, etc. Special privileges are those that require additional training, usually procedures. Some of the latter may become core privileges over time.
Special privileges are needed for anything “infrequent and high risk,” which requires some judgment – i.e. if a procedure is not listed, does that mean you cannot do it, or that it does not even require special privileges? Which procedures are listed is determined by the judgment of the clinicians in medical staffing, and the list is not always perfect.
All of these processes are hospital based, usually not part of state law, and are also often subject to Joint Commission regulation. However your hospital handles them, it is expected to follow its own policies consistently.
Learners are managed under policies for proctoring, not privileges. A person with procedural privileges can generally supervise a learner without privileges to perform it; if that’s a student, it is considered to be “done” by the proctor, and if by a licensed provider without privileges, it is “done” by the learner under supervision. Such a learner may eventually obtain their own privileges (usually by meeting a requirement of either numbers or observed competence or both). The exact rules of how all this works is governed by a proctoring policy which can be looked up.
While many providers may feel it is accepted, or even an ethical obligation, to perform procedures they are trained but not privileged to perform in an emergency (i.e. to save a life when a privileged person is not immediately available), there is usually no explicit allowance for this in hospital policy, so buyer beware.
If you don’t like how your processes work, change them.

Lightning rounds 60: The nuances of insulin, with Melissa Nestor

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We chat with Melissa Nestor, clinical pharmacist in neurocritical care, about tho subtleties of glucose and insulin management in the ICU.

Learn more at the Intensive Care Academy!

Episode 98: Running rapid responses

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We discuss the practicalities of running a rapid response, including crowd management, coordinating with primary services, working outside the ICU, and rapidly obtaining and synthesizing diagnostic data.

Learn more at the Intensive Care Academy!

Lightning rounds 59: The nuances of nebulizers, with Keith Lamb

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We explore the practical intricacies of nebulized medications, including timing, dosing, types of devices, and more, with Keith Lamb (@kdlamb1), RRT, RRT-ACCS, FAARC, FCCM.

Learn more at the Intensive Care Academy!

Episode 97: Managing ICP crisis

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We explore the practical basics of managing an elevated ICP with impending herniation, including EVD troubleshooting, hyperosmolar therapies, and the role of craniectomy.

Learn more at the Intensive Care Academy!

References

ENLS tiers

Episode 96: Understanding ammonia, with Prem Kandiah

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With Dr. Prem Kandiah, neurointensivist, transplant intensivist, and ammonia enthusiast, we explore the physiology of hyperammonemia, the nuances of its measurement and interpretation, and unpack some less-recognized causes, including infection by urease-producing organisms and malnutrition/gastric bypass.

Learn more at the Intensive Care Academy!

References and resources

Kamel, A.Y., Shah, P., Pipek, L.Z. et al. Nutritional Emergencies. Curr Surg Rep 13, 30 (2025). https://doi.org/10.1007/s40137-025-00465-9:
Hyperammonemia cheatsheet from Prem:

Work Up and Rx for hyperammonemia31 Download

Acute Liver Failure

Overall management of ALF

Bernal, W. and J. Wendon, Acute liver failure. N Engl J Med, 2014. 370(12): p. 1170-1.
Bernal, W., et al., Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol, 2013. 59(1): p. 74-80.
Kandiah PA, Nanchal R, Subramanian RM. Acute Liver Failure. In: Schmidt GA, Kress JP, Douglas IS. eds. Hall, Schmidt and Wood’s Principles of Critical Care, 5th Edition. McGraw Hill; 2023. Accessed August 09, 2023.

CRRT in ALF

Warrillow S, Fisher C, Tibballs H, et al. Continuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure. Crit Care Resusc 2020;22:158-165.
Cardoso FS, Gottfried M, Tujios S, Olson JC, Karvellas CJ, Group USALFS. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology 2018;67:711-720.

Osmolar Shifts in ALF

Liotta EM, Romanova AL, Lizza BD, Rasmussen-Torvik LJ, Kim M, Francis B, et al.
Osmotic shifts, cerebral edema, and neurologic deterioration in severe hepatic encephalopathy. Crit Care Med. (2018) 46(2):280–9. doi: 10.1097/CCM.0000000000002831

Ammonia toxicity in Liver Failure

Dasarathy S, Mookerjee RP, Rackayova V, Rangroo Thrane V, Vairappan B, Ott P, et al. Ammonia toxicity: from head to toe? Metab Brain Dis. (2017) 32(2):529–38. doi: 10.1007/s11011-016-9938-3
Guo, R.M., et al., Brain MRI findings in acute hepatic encephalopathy in liver transplant recipients. Acta Neurol Belg, 2018. 118(2): p. 251-258
Kumar G, Taneja A, Kandiah PA. Brain and the Liver: Cerebral Edema, Hepatic Encephalopathy and Beyond. Hepatic Critical Care. 2017 Aug 7:83–103. doi: 10.1007/978-3-319-66432-3_8. PMCID: PMC7122599.

Ammonia in Cirrhosis

Gallego JJ, Ammonia and beyond – biomarkers of hepatic encephalopathy. Metab Brain Dis. 2025 Jan 15;40(1):100. doi: 10.1007/s11011-024-01512-7. PMID: 39812958; PMCID: PMC11735499.

Ammonia in in post bariatric surgery hyperammonemia

Kamel AY, Shah P, Pipek LZ, Shah A, Kandiah PA. Nutritional Emergencies. Current Surgery Reports. 2025;13(1):30. DOI10.1007/s40137-025-00465-9

Post Lung Transplant Hyperammonemia

Kamel, A.Y., et al., Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series. Transpl Int, 2022. 35: p. 10433.

Post cardiac arrest Hyperammonemia

Nojima T et al. Can Blood Ammonia Level, Prehospital Time, and Return of Spontaneous Circulation Predict Neurological Outcomes of Out-of-Hospital Cardiac Arrest Patients? A Nationwide, Retrospective Cohort Study. J Clin Med. 2022 May 4;11(9):2566. doi: 10.3390/jcm11092566. PMID: 35566692; PMCID: PMC9105173.

Ammonia Bowel Ischemia

Watari M et al. Ammonia determination as an early indicator in experimental superior mesenteric artery occlusion. Hiroshima J Med Sci. 1997 Dec;46(4):159-67. PMID: 9538566.

Study on undifferentiated causes of hyperammonemia

Maquet J et al. Clinical, biochemical, and molecular findings in adults with hyperammonemia: A French bi-centric retrospective study. Mol Genet Metab. 2025 Sep-Oct;146(1-2):109223. doi: 10.1016/j.ymgme.2025.109223. Epub 2025 Aug 13. PMID: 40834544.

Sakusic A, Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU. Crit Care Med. 2018 Sep;46(9):e897-e903. doi: 10.1097/CCM.0000000000003278. PMID: 29985210; PMCID: PMC6095817.

Takeaway lessons

Effective ammonia clearance requires liver function, kidney function, gut function, and presence of skeletal muscles. It can also be compromised by A-V shunting bypassing the portal venous system (i.e. from enteric to systemic circulation; ask your radiologist to look for this as they may not otherwise report it).
Measuring the plasma ammonia level is not too technically difficult, but does have a time limit; allowing a sample to sit may falsely elevate the result. It’s therefore tough to do for outpatients. For inpatients, however, unless it gets forgotten on a table, it is generally not so difficult. Arterial vs venous doesn’t matter.
The peak ammonia on admission for cirrhotics is not as relevant as their cumulative ammonia burden over time (though of course this is not measurable). While difficult to interpret for those patients, a very high number is still very toxic, a very normal level probably absolves hepatic encephalopathy as a cause of altered mental status, and trending a number in between may help confirm response to therapy (eg the number should come down). A persistently elevated ammonia despite adequate catharsis may indicate need for a more aggressive regimen, or other attention to the underlying cause; a common cause would be a patient with GI bleeding, where persistent blood in the gut can cause persistent ammonia elevation.
Everyone agrees that ammonia should be followed in acute liver failure, where it correlates closely with risk of cerebral edema.
Checking ammonia in the patient without clear liver failure, but unexplained altered mental status, is reasonable—though an abnormal result will require a thoughtful approach to explaining it.
Cardiac arrest, especially with prolonged resuscitation, will reliably increase the ammonia level (if measured during or immediately after), as a direct effect of global ischemia.
Gut ischemia can elevate ammonia. Enterocytes require glutamine for energy; by interrupting this pathway, they may generate ammonia via anaerobic metabolism, much as other cells might generate lactate.
Medications, particularly valproate, can elevate ammonia.
Any elevated muscle activity or muscle breakdown, such as seizure or rhabdomyolysis, can generate nitrogen and hence transient hyperammonemia.
Any sarcopenia predisposes to hyperammonemia, as skeletal muscle is too sparse to reliably clear ammonia.
Inborn errors of metabolism involving the urease cycle are uncommon in adults but something to consider, especially if genetic testing is available to you.
Severe malnutrition, most often due to gastric bypass, can cause hyperammonemia. This is probably due to multifactorial causes, including sarcopenia and muscle catabolism, but malnutrition seems to induce a true hepatic steatosis is well (reversible if nutrition is restored). Radiographically and clinically this looks like MAFLD/MASH, but is not caused by metabolic syndrome or obesity, but the opposite state of malnutrition. (This phenomenon is also seen in Kwashiorkor.) Probably this is due to some synthetic dysfunction affecting beta oxidation and lipid metabolism, and/or absence of essential fatty acids—not clear.
Urease-producing bacteria can generate ammonia. This will usually be transient, since antibiotics will readily kill them. However, with a deep-seated infection such as an abscess, this may not be true and should be considered as an ongoing ammonia source. Examples include: Staph epidermidis and Staph saprophyticus, Helicobacter Pylori, Klebsiella, Nocardia, Cryptococcus, Pseudomonas spp., Corynebacterium, Proteus penneri, Providencia stuartii, and Morganella morganii
An especially important urease producer is ureaplasma, an atypical organism similar to mycoplasma, usually causing UTI or even STI. This will often not cause other signs of clinical infection, but can be a cause of ammonia production, and will not be grown on routine cultures (PCRs are needed on urine or BAL, or the Mayo Clinic has a blood PCR—all send-outs), nor covered with routine antimicrobials (atypical coverage, such as doxycycline, azithromycin, or levofloxacin is needed). This infection mostly occurs in the immunosuppressed, such as transplant patients, where it can cause occult pneumonia (an important and morbid cause of post-transplant hyperammonemia); consider it as well in anybody on rituximab or similar immunosuppression. It can also cause “sterile” joint effusions, so a patient on rituximab whose joint is tapped and grows inflammatory-but-aseptic fluid may be presumed to have progression of an underlying rheumatologic disease, have their immunosuppression escalated, and then end up with disseminated ureaplasma.
For the hyperammonemic due to malnutrition/gastric bypass: nourish with glucose and fats while limiting or holding protein completely in the acute period. This can be parenteral initially, as it’s easy to titrate protein in that fashion. Check and/or supplement everyone with micronutrients likely to be insufficient: high-dose thiamine, B6, L-carnitine, copper, zinc. Once ammonia stabilizes and clears, start to introduce protein cautiously, with the goal of eventually restoring an anabolic state to reverse the underlying steatosis. Go slow weaning everything to avoid rebounds.
Refractory hyperammonemia can be treated with dialysis (CRRT), though data is limited in this setting. Starting earlier may make sense, as osmolar clearance may be rapid once initiated and could precipitate cerebral edema if the osm load is already high. Some would add hypertonic saline with CRRT to try and mitigate this rapid osm drop, a common tactic in the ALF realm.
A common cause of proximal decompensation for these people is when micronutrient deficiencies starts to reduce gut motility, leading to poor tolerance of oral nutrition and anorexia. Once you fix these and the gut allows oral intake, their nutritional status can improve.
Lactulose and rifaximin can have some temporizing role in these patients, but a very short-acting one. They may also tend to worsen nutrition by accelerating gut transit time and filling the small-volume stomach.
The urease cycle scavengers sodium phenylacetate-sodium benzoate may help accelerate clearance of ammonia, if renal function is intact (they convert ammonia to PAGN which can be renally cleared). However, they are not a magic solution, take time to work, and do not address the underlying problem.