Does my patient have hepatorenal syndrome?

This is intended to provide a quick list for diagnosis of HRS, since HRS is a diagnosis of exclusion and should only be made once other conditions are “ruled out.” HRS is a clinical diagnosis, and there is no one perfectly sensitive or specific test. But if your patient meets these criteria, you should be worried.

  1. Ascites is present
  2. There is an AKI (creatinine >1.5)
  3. Rule out infection: there is no UTI or pyelonephritis
  4. Rule out prerenal injury: there is no improvement in serum Cr after resuscitation with 2 days of 1 mg/kg albumin, 100 g max
  5. Rule out intrinsic disease: there is no hematuria (>50 RBCs) or proteinuria (>0.5 g) to suggest renal disease
  6. Rule out meds: no nephrotoxic meds recently given
  7. Rule out hypotension/ATN: no signs of ATN in the urine, no shock or profound hypotension

In the past, there were minor criteria including oliguria (<0.5 L urine output/day), low urine sodium (<20), and low serum sodium. These were found to have poor specificity and were dropped in 2007.

There are two types of HRS: Type 1 is rapid (develops in <2 weeks) and severe, with a 10% survival rate over 3 months. Type 2 is more gradual and on a spectrum with diuretic-resistant ascites.

You should also ask yourself: what triggered this episode of HRS? Common precipitants include infection (check a chest x-ray for pneumonia, urine studies for UTI, blood cultures, and rule out SBP), prerenal causes (not giving enough albumin after large-volume paracentesis, diuretics), post-TIPS, and nephrotoxic drugs.

Advertisements

Help with transplant immunosuppressant maintenance regimens

Immunosuppressants aim to prevent this from happening:

Screen Shot 2017-01-29 at 3.52.15 PM.png
Organ rejection.

But too much immunosuppression can cause this:

Screen Shot 2017-01-29 at 7.16.22 PM.png
Drug toxicity and dead fish.

That’s why people can’t just be on ONE immunosuppressant after transplant: the doses required would be too toxic, so the effect is spread out over 2-3 medications.

Considering that the historical option was total body irradiation, we’ve come a long way. Azathioprine was the first chemical immunosuppressant, but cyclosporine, which came onto the scene in the 1970s, revolutionized kidney transplant survival rates.

***One of my chiefs last year made an amazing figure on maintenance transplant immunosuppression. It is worth this whole post and I highly encourage you to take a look!***

For us peons, what are the commonly used immunosuppressants? 

Mechanism of Action Starting doses Monitoring required Side effects
Tacrolimus (Prograf) Calcineurin inhibitor (CNI) 0.075-0.2 mg/kg/day Cr, drug trough Neurotoxicity, nephrotoxicity, diabetes, alopecia *many drug interactions
Cyclosporine (Neoral) Calcineurin inhibitor (CNI) 2-6 mg/kg/day Cr, drug level Neurotoxicity, nephrotoxicity, diabetes, hypertrichosis, gingival hypertrophy
Mycophenolate mofetil ## (CellCept, MMF) Purine analogue, prevents T cell proliferation 500-1000 mg daily CBC, drug trough GI/diarrhea, myelosuppression, lymphoid neoplasm *many drug interactions, needs dose adjusted for renal failure
Azathioprine (Imuran) Purine analogue, prevents T cell proliferation 1-3 mg/kg/day (maintenance) CBC, LFTs, Cr, check TPMT Nausea/vomiting, myalgias, leukopenia, transaminitis
Sirolimus (Rapamycin) mTOR inhibitor Weight based; 1-5 mg/day (maintenance) Drug level Pneumonitis, arthralgias, edema, hypertension, bone marrow suppression, hyperlipidemia
Everolimus (Afinitor) mTOR inhibitor 0.75-1 mg twice daily Drug level arthralgias, edema, hypertension, bone marrow suppression, hyperlipidemia
Prednisone The dozens of things steroids do Varies widely, minimum 7.5 mg every other day or 5 mg daily n/a Osteopenia, diabetes, headache, Cushing’s, weight, cataracts, psychosis (and many others)

## Mycophenolate can be either mycophenolate mofetil vs. sodium. The difference is that the sodium formulation (Myfortic) is an enteric capsule that may prevent some GI effects like diarrhea(?) but the jury is still out.

What are the major side effects of immunosuppression?

screen-shot-2017-01-29-at-7-04-46-pm
From the National Kidney Foundation

What is the underlying biology? ***This is a gross oversimplification.

Normally, T cells go scouting and if they encounter an antigen-presenting cell with foreign material on it, a chain reaction of events is started: calcineurin is activated, leading to a surge of IL-2 and its receptor, IL-2R, which upregulates the mTOR pathway, which leads to DNA nucleotide synthesis so that the T cell can multiply and generate an immune response.

Notice that the bolded words are the targets of the 6 immunosuppresants in the chart above.

Transplant pharmacology is REALLY COMPLICATED and you can do an entire fellowship training program for this. This is an excellent, but 100-page document from a Canadian transplant website. Here are two organ-specific guides/reviews regarding immunosuppression:

When should a PPI be stopped?

There are a few reasons why patients are started on PPIs in the inpatient setting: in the setting of an acute upper GI bleed; long periods of no oral intake; high doses of steroids that require PPI prophylaxis. The problem is that when these patients are discharged, the PPI is often carried forward as a “new medication” that is then carried forward by outpatient providers, even if the indication for which they were started on PPIs has resolved.

PPIs should be continued in patients with Barrett’s esophagus, hypersecretory states (Zollinger Ellison), symptomatic GERD, and patients at high risk for bleeding (on NSAIDs, cirrhotics). But just because someone has had bleeding or a peptic ulcer doesn’t mean they have to be on a PPI for life! For low-risk patients with a first-time ulcer, you should reassess whether they need to continue a PPI 2 months afterwards. The PPI should be stopped when the acute indication has passed or, in the case of GERD, the patient has been asymptomatic for about 3 months. The lengths of time depends: Up To Date says, “As a general rule, active duodenal ulcers should be treated for four weeks and gastric ulcers for eight weeks.”

It is important to periodically assess whether a patient is a candidate for tapering and discontinuing their PPI because there are a number of downsides to PPIs:

  • increased susceptibility to gastroenteritis and C. diff infections
  • decreased absorption of vitamin B, iron, and calcium
  • decreased calcium absorption then has implications for osteoporosis
  • ?increased risk of aspiration pneumonia

Esophageal pH testing can be used to prove that someone does not have GERD, but it can be a bit cumbersome to arrange. The most important factors to consider are someone’s symptom profile and their risk for becoming symptomatic or bleeding in the future.

See this ACP Internist article about strategies for stopping PPIs. If a patient complains of “acid rebound” following taper of PPI, then they likely have symptomatic GERD and should actually continue their PPI.

How helpful is NG lavage for diagnosing an upper GI bleed?

It has traditionally been taught that one of the first steps in managing an upper GI bleed is to place an NG tube to see if there are bloody aspirates. While it’s true that if you get a bloody aspirate, there is more likely to be an actively bleeding lesion, the data on whether the NG tube changes management is not too supportive.

In a Journal Watch post from 2011, David Bjorkman reviews a VA study of over 600 patients with suspected GIB. The study found that while placing an NG tube got patients faster care, it didn’t change clinical outcomes or rate of complications. He writes: “We already know that NGL cannot be used to exclude ongoing upper GI bleeding as one sixth of patients with active bleeding will have a negative NGL. Now, this study demonstrates that NGL results in no difference in a number of important clinical outcomes.”

However, if you are an ED provider, you may think differently about placing an NG tube. It may help you triage patients better in terms of who needs to be seen by GI first and whether there is evidence of a SEVERE bleed. Here is some evidence from the EM side of things.

The (f)utility of inpatient guaiac/fecal occult blood tests

Here’s a situation that most of us have probably encountered:

Intern: Mrs. Jones’s hemoglobin is drifting down…her baseline is 12 and today it’s 10. She’s hemodynamically stable and doesn’t show any signs of bleeding.

Attending: No signs of bleeding, eh? Let’s guaiac her.

Intern: *dies a little inside*

There is one, and only one appropriate indication for a stool guaiac, and that is for colon cancer screening in someone who for one reason or another cannot undergo colonoscopy. In a recent Australian study in the Journal of Internal Medicine, out of 461 inpatients who were guaiac’ed, only 1 patient was appropriately screened for colon cancer. 16% of the patients had their care delayed or somehow adversely affected because of a positive result that necessitated consideration for endoscopy. Another study shows that inpatient FOBTs are a quality improvement issue–if you’re not going to act on a positive result, why bother getting a test that the patient will get charged for?

Here are a few more fun facts:

  • We all shed about 0.5-1.5 ml of blood into stool over 24 hour period. A guaiac can detect an amount of blood as small as 2 ml to 10 ml of blood in the stool per 24hrs.
  • To reduce the rate of false positives, a patient should be on medication and diet restrictions: 72 hours off medications like NSAIDs or aspirin or vitamin C; off red meat, cantapoupe and other melons, grapefruit, turnips, broccoli, figs, radhish, horseradish, cauliflower, cabbage, cucumber, carrot, potato, pumpkin, zucchini, parsley.
  • A FOBT costs the patient anywhere from $20-60. And the discomfort of a rectal exam.

What is the management and treatment for H. pylori?

url.jpg

Not to belabor second-year pathophysiology courses, but first, a couple of lines about what H. pylori actually is. It’s a flagellated bacteria found in water that is spread by the oral-fecal route and preferentially burrows into the mucosal surface of the stomach, where it causes toxic effects through ammonia production and causing antral cells to react by producing more gastrin, overabundance of parietal cells, and acid. It can lead to chronic gastritis and encourage development of ulcers and even cancer.

Also, the story of how it was discovered is pretty cool, although definitely not IRB-approved.

Who should be tested for H. pylori? 

  • People <55 who have dyspepsia (but no alarm symptoms that require further workup!)
  • long-term PPI therapy
  • unexplained iron or B12 deficiency
  • A past or present diagnosis of peptic ulcer disease
  • gastric MALT lymphoma

What’s the best way to diagnose H. pylori? There are several methods available: serum, stool, breath test, biopsy. Each has pros and cons, but here are a couple of key points. The breath test is both highly specific and sensitive. Biopsy is actually not as accurate (because of sampling error) but is helpful to do if you’re doing an EGD anyway, and can be used to see if there is any associated gastritis or ulcer formation. The serum test is also not as reliable (can’t distinguish between past and present infection). Patients with recent GI bleeding or who are already on PPI therapy may have false negative results.

What are the treatment regimens?

Triple therapy is most commonly prescribed in the US. It consists of: PPI BID, amoxicillin 1 g daily, and clarithromycin 500 mg BID for 7-14 days. Metronidazole can be substituted if there is a penicillin allergy. However, if triple therapy fails, quadruple therapy should be used: PPI, bismuth, and two antibiotics, usually tetracycline and metronidazole.

It should be noted that initial treatment fails in 20-30% of patients, and so there are a number of alternatives, like using doxycycline, levofloxacin, and various other agents.

Who should get retested for confirmation of eradication?

  • persistent symptoms despite treatment
  • people found to have H.pylori-associated peptic ulcer or MALT lymphoma
  • this should take place >4 weeks after treatment ends

What is cecal intubation?

Sometimes on a colonoscopy report, you may see a line that goes something like, “The colonoscope was introduced through the rectum and advanced under direct visualization until the cecum was reached.” This means that cecal intubation was done.

Cecal intubation is defined as passage of the colonoscope tip to a point proximal to the ileocecal valve, so that the entire cecal caput, including the medial wall of the cecum between the ileocecal valve and appendiceal orifice, is visible. It is a quality metric for colonoscopy because otherwise you may miss a substantial number of proximal polyps. Low cecal intubation rates have been associated with higher rates of interval proximal colon cancer.