Here are some of my favorite hyperkalemia pearls that will help take your understanding of the disease process to the "201" level!

And, yes, this ominous banana is meant to be an abstract visualization of the serious consequences of hyperkalemia.

Read on!

- Thread -

Only 2% of total body K is extracellular.

In HyperK, the resting membrane potential becomes LESS negative, leading to downstream effects on electrical conductivity.

Chronic changes in extracellular K lead to compensatory mechanisms to reduce this excitability.

https://twitter.com/ROKeefeMD/status/1743256123019526364?s=20

Under normal conditions, 90% of potassium is eliminated renally, and 10% is eliminated in stool.

The most common cause of HyperK presenting to the hospital is decreased renal function or missed dialysis.

Diet is usually only a factor in those with reduced renal function.

Healthy kidneys can excrete up to 400 mEq of potassium each day.

The average potassium intake of ~2,000 to 3,500 milligrams (mg) per day translates to approximately 51 to 90 mEq (mmol) per day.

https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/

Common foods high in potassium

- Potatoes
- Dairy
- Cereals and Bran
- Bananas
- Avocados
- Leafy green veggies

https://www.kidney.org/sites/default/files/NKF_Guide_to_Low_Potassium_Diet_Final_0.pdf

If you really want to get into the weeds, bananas contain 1.5-2.0 mEq of potassium per inch.

Thus, the average banana has ~12 mEq.

Shout out @nickmmark for those pearls!

https://x.com/nickmmark/status/1714630670121935004?s=20

ACE/ARBs, MRAs, NSAIDs, and TMP-SMX can all lead to HyperK by lowering the release/effect of aldosterone.

Through the complex process of RAAS, aldosterone leads to sodium retention and potassium excretion, mostly at the distal convoluted tubules.

Acidosis causes HyperK by messing with the Na/H antiporter and the sodium gradient, which in turn reduces the activity of the Na/K-ATPase pump.

Insulin, on the other hand, stimulates the Na/K-ATPase pump, leading to more K going into the cell.

If a patient is in DKA, they may be hyperkalemic since insulin is not present to push potassium into cells.

But TOTAL body K will be low.

So you need to replete K when less than ~5.2 mEq/L and hold insulin if less than ~3.3 mEq/L to prevent a dangerous hypokalemia.

VBG/ABG K levels may not perfectly correlate with the BMP but should be within ~0.5 mEq/L.

Hemolysis in vitro as part of the blood drawing process can lead to "pseudohyperkalemia".

Most labs will report this as “hemolyzed” rather than as an inaccurately high level.

Severe or acutely elevated K is more likely to be symptomatic; those with chronic elevations will often be asymptomatic and diagnosed incidentally.

The weakness associated with hyperkalemia often starts in the legs and then progresses to the arms (ascending paralysis).

Calcium gluconate should reverse EKG changes in 5 minutes; if not, push again.

Calcium chloride has a higher risk of tissue necrosis at the IV site and should be given centrally.

Calcium salts have no actual effect on K levels, and don’t last more than 30-60 mins.

Temporizing/redistributing can drive the K down ~0.5-1.5 mEq/L in the short term.

Inhaled SABA (albuterol) should not be used as a monotherapy and is less likely to work in patients taking beta blockers or with CKD.

Elimination via furosemide or Lokelma requires urine or stool output.

If the patient cannot do either, the only other way to eliminate potassium is via dialysis.

However, elimination is not required in all patients - especially if the acute insult has been addressed.

Cation-exchange resins like kayexalate and lokelma work by releasing sodium ions which are in turn exchanged with potassium in the gut.

Resins commonly lead to constipation and should be given with laxatives.

Sodium polystyrene sulfonate (Kayexalate) has been shown to have rare but serious adverse effects, specifically gut necrosis.

https://pubmed.ncbi.nlm.nih.gov/31180477/

You can read the unrolled version of this thread here: https://typefully.com/ROKeefeMD/jigygY6

Hyperkalemia and Potassium Pearls

Picking up hyperkalemia on an EKG can be lifesaving.

We all know about "peaked T-waves," but the underlying pathophysiological basis for the various EKG changes is confusing and unintuitive.

A thread on EKG findings in hyperkalemia!

- Thead -

Disclaimers

Though these are the "classic" EKG changes, patients do not necessarily progress in this order.

EKGs do not always correlate with the actual K level - it depends on the chronicity of the elevation.

Lastly, EKG changes are NOT sensitive for hyperkalemia.

Why does HyperK lead to EKG changes?

The "less-negative" membrane potential initially leads to excitability

It then leads to incomplete or delayed depolarization

Lastly, zones of differential excitability form, leading to reentrant circuits or uncoordinated contraction

Some key pearls to appreciate:

1. Atria are more susceptible to changes in K. This is why we see effects on the PR interval and p-waves earlier than in the QRS.

2. HyperK is one of the "H's and T's" etiologies of cardiac arrest. It can lead to VFib, PEA, or asystole.

Here are the "classic" EKG changes, courtesy of @LITFLblog and @Core_EM (their excellent blog posts linked at the end of the thread!)

1. Peaked T-waves

2. Prolonged PR and flat p-waves

3. Sinusoidal Wave or life-threatening arrythmia

Let's discuss each.

1. Mild: K 5.5-6.5 mEq/L

Peaked T-waves

The earliest change associated with hyperK is accelerated REpolarization of ventricular cells.

This is due to more outward K current in repolarization and more cells repolarize at the same time, creating the sharp, steep T-waves.

This first phase seemed unintuitive to me.

If there is more K outside the cell already and the concentration gradient is now "less negative," why would more K leave the cell?

It's because we are talking about REpolarization and not DEpolarization.

Despite a reduced gradient, the cells are closer to the threshold potential, so they are able to return to their resting state more quickly.

K channels may also become more active or open longer due to the altered membrane potentials, facilitating efflux.

2. Moderate: K 6.5-8.0 mEq/L

Prolonged PR Interval
Flattened P-waves

At these levels, the DEpolarization of the atria begins to be affected, leading to prolonged PR (delayed conduction from the atria to the ventricles).

Eventually, the p-waves flatten and disappear.

QRS Widening

The QRS represents ventricular depolarization. As the speed of ventricular depolarization decreases, conduction across the ventricle is decreased, widening the QRS.

At higher levels, the QRS becomes so long that it merges with the T-wave.

Again, unintuitive.

If the cells are more excitable with "less negative" potentials, why would PR increase and p-waves go away?

As hyperK progresses, the resting membrane potential becomes so depolarized that it leads to the inactivation of voltage-gated sodium channels.

These sodium channels are crucial for initiating an action potential.

Thus, when they are inactivated, it becomes difficult to initiate a new action potential.

The AV node is particularly sensitive, resulting in a prolonged PR interval.

3. Severe: K > 8.0 mEq/L

Sine Wave Pattern

Severe disturbances of depolarization and repolarization lead to the complete joining of the QRS complex and T-wave.

Commit these images to memory. You may save someone's life.

VFib and Arrythmias

In zones of differential excitability, some areas may respond quickly to an electrical impulse, while others respond more slowly or not at all.

This can lead to uncoordinated contraction of the venticular muscle (resulting in VFib or PEA).

These @LITFLblog and @Core_EM blogs are excellent, and are the source of the images included in this thread.

https://litfl.com/hyperkalaemia-ecg-library/

https://coreem.net/core/management-of-hyperkalemia/

Here are some of my favorite posts about EKG changes and HyperK from the MedTwitter community!

First, @EM_RESUS - my go-to educational source for all things related to EM and EKGs!

"Slow VTach" may be hyperK!

https://twitter.com/EM_RESUS/status/950058330118074369

The "hyperkalemia box".

Thanks @sargsyanz for helping to promote this awesome memory trick!

https://twitter.com/sargsyanz/status/1221667215033978880

@jtrebach - not only a master educator, but always good for a laugh!

https://twitter.com/jtrebach/status/1658863296986988549

A fantastic visual representation of the EKG changes with hyperkalemia.

https://twitter.com/ThatSleepDoc/status/1353504737619013635

"The 4 P's" - a great way to remember the key EKG changes in hyperK!

@DxRxEdu

https://twitter.com/DxRxEdu/status/1545057992764117001

You can read the unrolled version of this thread here: https://typefully.com/ROKeefeMD/fobOWaS

Understanding EKG Findings in Hyperkalemia

Hyperkalemia gets so much attention because it's a common, complex emergency with potentially life-threatening cardiac implications.

Here's my approach to working up and managing HyperK in the hospital, along with some key pathophys everyone should know!

- Thread -

Check out these @pointofcaremed digital resources on hyperkalemia for use at the point of care!

Online Template
https://www.pointofcaremedicine.com/inpatient/hyperkalemia

Podcast
https://podcasters.spotify.com/pod/show/pointofcarepodcast

YouTube
https://youtu.be/8CW4ryTJshs?si=wUkDoOy8rNoOwd1o

Though cutoffs vary, HyperK is generally considered to be a K > 5.5 mEq/L

Symptoms usually aren't present until K > 7.0 mEq/L or if the level rises rapidly due to an acute insult.

HyperK is present in ~2-3% of the population, but up to 50% in those with CKD!

Why do we take HyperK so seriously?

Potassium influences resting membrane potential, and HyperK can lead to increased excitability of cells.

The most dangerous consequence of this includes cardiac arrythmias (look out for a future thread on this)!

At baseline, resting membrane potentials are NEGATIVE but vary by cell type (neuron, muscle, cardiac, etc.) based on ion channels and ion pump activity.

At baseline, only 2% of total body K is extracellular, and this level is tightly regulated.

As such, there is more K INSIDE cells.

HyperK leads to more K OUTSIDE cells.

This makes the potential LESS NEGATIVE.

In other words, the potential becomes closer to zero (i.e -90 --> -80).

These changes lead to downstream issues with electrical conduction.

Hyperkalemia from acute insults is usually short-lived unless there is an ongoing or chronic process.

Common examples of these processes include:
- Renal disease
- Acidosis
- Hypoaldosteronism

Here's a checklist to use when admitting a patient with hyperkalemia.

STAT EKG - calcium gluconate if any changes

Gut Check - repeat (VBG okay for ballpark) to rule out pseudohyperkalemia

Triage for HyperK Emergency

Chart Check - known ESRD/dialysis

HyperK Emergency is present if one or more of:

1. K > 6.5 mEq/L

2. Clinical changes, including (not limited to): EKG changes, muscle weakness, paresthesias

3. An active process that may lead to persistently elevated K levels (ESRD, GI Bleed, rhabdo, TLS)

Here is the most pertinent info to collect for your HPI.

Common symptoms are all the result of changes in membrane potential.

If the patient has ESRD, it is important to know if they make urine. This will help determine which temporizing treatments may be efficacious.

Etiology/Differential Buckets

- Reduced Elimination (most common)

- Shifting into Extraceullar Space

- Extracellular Release

- Excess Intake from Diet

Acidosis can lead to HyperK

Why?

Acidosis messes with the efficacy of the Na+/H+ antiporter.

This leads to decreased intracellular Na+.

This gradient change impacts the efficacy of the Na/K-ATPase pump, which in turn leads to increased extracellular K.

Common meds that can cause hyperkalemia:

- ACE/ARBs
- MRAs
- NSAIDs
- TMP-SMX

All of these act by decreasing the effect of aldosterone.

Aldosterone primarily acts on distal tubules and leads to Na reabsorption and K secretion.

Other medications can redistribute K

Treatment of HyperK

Stabilize:

- If EKG changes or emergency

- Calcium gluconate 1-2g q5 minutes until EKG normalizes. Only lasts 30-60 minutes.

Temporize:

- If emergency - NOT everyone

- Insulin 10 U (add dextrose if BG <250).

- Albuterol is only an add-on

Eliminate:

- If emergency OR concern the K will continue to rise

- If patient can urinate, give furosemide 40mg IV in naive patients.

- Give sodium zirconium cyclosilicate (Lokelma) 10mg TID if patient can make stool. Give with a laxative (can lead to constipation).

For monitoring in an emergency, once EKG changes have resolved:

- Trend EKG and K q2-4 hours
- Continuous telemetry

Remember that calcium gluconate only lasts 30-60 minutes and does not actually address the etiology of the underlying HyperK.

If You Remember Nothing Else

- Most common cause in the hospital is CKD/ESRD (missed dialysis)

- Emergency if > 6.5 mEq/L, clinical findings or EKG change, or an ongoing process causing HyperK

- Temporizing is not necessary in all patients

- Dialyze if all else fails

Here's my favorite review article on the workup and management of hyperkalemia.

https://pubmed.ncbi.nlm.nih.gov/33160639/

For making it this far, here's the Hyperkalemia Admission One-Pager with a checklist, HPI intake, differential, and sample EHR dotphrase.

You can also find the downloadable PDF on the @pointofcaremed website.

You can read the unrolled version of this thread here:

https://typefully.com/ROKeefeMD/MkRGJ90

Managing Hyperkalemia in the Hospital

Diabetic foot ulcers affect 15-25% of patients with diabetes over their lifetime.

Appropriate workup and management of diabetic foot wounds is a crucial skill for anyone interested in internal medicine.

Here are my top pearls on the topic!

- Thread -

First, I didn't appreciate how grim the prognosis is for patients with diabetic foot wounds.

Some stats:

50% of diabetic ulcers become infected

20% of diabetic foot infections lead to some type of amputation

The 5-year mortality after amputation is >70%

Shocking

If revascularization is not possible or unsuccessful and/or the tissue is necrotic or gangrenous and poses a risk to the patient’s life, amputation may be the only viable option for management.

Diabetic foot ulcers lead to over 1 million amputations annually.

The most important risk factors for the development of foot ulcers include poor glucose control, peripheral arterial disease (PAD), neuropathy, renal disease, smoking, the presence of a callus, and edema.

The pathophysiology of foot ulcers:

- Loss of sensation from peripheral neuropathy leads to repetitive, unnoticed traumas

- Motor neuropathy leads to abnormal walking and pressure points

- PAD leads to impaired wound healing

Hyperglycemia itself leads to the formation of advanced glycation end-products (AGEs).

AGEs prevent the migration of inflammatory cells to wounds and can cause direct microvascular damage.

The plantar surface of the metatarsal head is the most common location for foot ulcers.

Other common locations include the toes and heels.

These are common pressure points and sites of repetitive trauma.

Frequent foot exams are crucial.

This is the checklist I use when admitting patients with diabetic foot wounds.

Don't miss nec fasc, gas gangrene, osteomyelitis, or limb ischemia.

Ankle-brachial index (ABI) testing is often done prior to any procedures (i.e amputations) to assess for PAD and the need for revascularization to ensure proper wound healing.

Its compares the pressure in the ankle vs arm

PAD is severe if the ABI is less than 0.4

ABI can be affected by the presence of calcified or incompressible arteries, particularly in patients with diabetes or advanced age.

In such cases, the ABI will be > 1.4

Angiography may be needed to actually visualize blood flow and sites of stenosis.

Xrays can detect gas and the presence of bone changes in patients with diabetic foot wounds.

However, MRI is the most sensitive for diagnosing osteomyelitis.

MRI is 90% sensitive, 82% specific for osteomyelitis, with a high NPV

The LR is 0.14 if the MRI is normal

Erythrocyte sedimentation rate (ESR) is a non-specific inflammatory marker.

It measures the rate at which RBCs sediment in blood (mm/hr).

This reflects the level of plasma proteins (fibrinogen, immunoglobulins) which increase inflammation.

It rises and falls slowly

C-reactive protein (CRP) is a more specific marker for acute inflammation.

It’s a protein produced in the liver in response to inflammation.

It rises and falls quickly and the levels aren’t impacted by plasma components.

It is useful for monitoring response to treatment

Osteomyeltitis without source control (i.e amputation) is usually treated with at least 6 weeks of antibiotics guided by cultures from a bone biopsy.

If source control is achieved, treatment can be much shorter, often 2-5 days.

I found this brief thread highlighting some key takeaways from the 2023 guidelines to be really helpful!

Thanks @Factor_XII !

https://twitter.com/Factor_XII/status/1719094302939455940

Link to the guidelines: https://pubmed.ncbi.nlm.nih.gov/37779323/

My favorite review articles on the topic:

A @JAMA_current Review from 2023
https://pubmed.ncbi.nlm.nih.gov/37395769/

A @NEJM Review from 2017
https://pubmed.ncbi.nlm.nih.gov/28614678/

As always, here's the One-Pager for admitting patients with diabetic foot wounds!

You can download a PDF version on the @pointofcaremed website.

And here's the full video breaking down a systematic approach to admitting patients with diabetic foot wounds!

https://twitter.com/ROKeefeMD/status/1732885333480448438

You can find all of the full episodes on Spotify and YouTube!

You can read the unrolled version of this thread here: https://typefully.com/ROKeefeMD/GU4MnRk

Diabetic Foot Ulcers - Pearls for Workup and Management

In acute gout flares, there's more than meets the eye!

A deep dive reveals a fascinating story of unusual pathophysiology and a number of unintuitive clinical pearls!

Read on for some surprising truths and practical tips for management!

- Gout 201, A Thread -

Check out these @pointofcaremed digital resources on Gout Flare for use at the point of care!

They include admission checklists, HPI intakes, differentials, sample dotphrases, and key clinical pearls, along with a podcast and YouTube video with accompanying slides.

If you're like me, when you think about gout, you see those negatively birefringent crystals in synovial fluid - STEP 1 stuff.

I thought that gout flares only happen when urate levels rapidly increase and crystals start to form in the synovium.

But there's more to it!

Gout is characterized by the chronic deposition of monosodium urate crystals into the synovium.

The "solubility threshold" for monosidum urate is ~6.8 mg/dL, above which circulating uric acid can turn into crystals.

This can constantly happen without causing a flare!

Hyperuricemia is necessary but not sufficient to cause gout.

Almost all UA is filtered at the glomerulus, but ~90% is reabsorbed.

Humans don't make uricase, so all formed UA must be excreted.

Hereditary underexcretion of UA is the most common cause of hyperuricemia.

Acute gout flares can happen when there is increased deposition OR mobilization of already present crystals within the joint.

The "free-floating" crystals are ingested by neutrophils which activate inflammatory pathways via the NLRP3 inflammasone and production of IL-1B.

A sudden increase OR decrease in uric acid levels in blood can lead to a flare!

A decreased uric acid level can lead to mobilization of deposits already present in the joint.

This is why starting allopurinol to lower uric acid levels can precipitate a flare!

A sudden increase in uric acid can also start a flare.

When consumed, purines are metabolized into uric acid.

Some of the most purine-rich culprits include:

- organ meat (liver)
- beer and other alcohol products
- seafood
- red meat
- high-fructose soft-drinks

Beer consumption is especially suited to provoke a gout flare because:

- Yeast cells contain high purine content

- Alcohol metabolites compete with uric acid to be excreted by the kidneys

- Alcohol is a diuretic, contributing to dehydration

Note the alcohol in the pic!

URAT1 (Urate Anion Transporter 1) is a protein transporter in the proximal tubule of the kidney.

Overactive URAT1 is commonly implicated as a genetic variant that can increase the risk of gout.

Diuretics lead to conditions that can increase the activity of URAT1!

Gout flares are more common at night.

Why? Because three things are more likely to happen at night that support the deposition of uric acid or lessen the body's ability to stave off inflammation.

1. Lower body temperature
2. Dehydration
3. Noctural dip in cortisol

Understanding all this key background pathophysiology can help inform how you approach the workup and management of acute flares!

Here's an admission checklist!

Key points:

- Determine if you need synovial fluid

- Rule out septic joint

- Start treatment ASAP!

Here is the most pertinent info to collect for your HPI!

Key things:

- Prior flares
- Onset of this flare
- Signs/symptoms - pain, swelling, warmth, erythema, reduced ROM
- Involved joints
- Allopurinol use and adherence
- Narrow in on possible trigger

Podagra is a painful/inflamed MTP joint at the base of the big toe.

It originates from Greek.

"Pous" means "foot" and "Agra" means "trap", aptly describing the sudden and severe pain of a gout flare, as if the foot has been caught in a trap!

Podagra is the first symptom in 50% of early gout flares.

But why this joint specifically?

In short, we don't know.

Possible reasons:

- MTP is coolest joint
- Big toe subject to repetitive trauma
- Synovial lining may be more susceptible
- Higher UA concentration

As gout progresses, it is more likely to involve other joints such as the knees or hands.

Tophi are aggregations of urate crystals and giant cells that are formed after repeated attacks and can cause deformities and arthritis of joints - commonly interphalangeal joints.

https://twitter.com/NEJM/status/1476885857239920640?s=20

Here's a relevant differential.

You can't miss a septic joint!

Be on the lookout in those with recent surgery or prosthetic joints.

Note that the presence of crystals does NOT rule out an infection! Always send cultures.

Calcium Pyrophosphate Deposition Disease (CPPD), or "pseudo-gout," is another crystalline arthropathy.

It's very common in patients over 80, but often asymptomatic.

CPPD flares more commonly involve the knees, wrists, and MCP joints.

CPPD is associated with hyperparathyroidism, hypothyroidism, hypomagnesemia, and hemochromatosis.

It more commonly involves the knees, wrists, and MCP joints.

You may see chondrocalcinosis on X-Ray due to deposition in cartilage.

Here's a sample plan for managing gout.

Key points:

- best to start therapy within 24 hours
- generally monotherapy
- colchicine reduces neutrophil activity
- NSAIDs and steroids reduce inflammation
- continue allopurinol if already on it
- ice packs

If left untreated, acute gout flares can last days to weeks, but they will always resolve on their own!

If gout is not treated early in its course, gout flares tend to become increasingly frequent and severe and are often polyarticular.

Uric acid levels at the time of a flare are rarely helpful.

Why?

- Uric acid may be actively forming crystals
- Inflammation lowers the level
- Acutely lower levels can also lead to the flare

Check ~2 weeks after the flare for a better sense of a patient's baseline.

Allopurinol should be started if:

- Greater than 2 attacks per year
- CKD3
- Baseline UA > 9
- Presence of tophi
- Radiographic evidence of joint damage

Make sure you are giving prophylatic anti-inflammatories when starting and uptitrating the doses to prevent a flare!

Start allopurinol at 50-100mg daily.

Titrate by 100mg weekly up to a max of 900mg daily.

Divide doses if giving >300mg daily.

The Goal UA is less than 6 (below the solubility threshold!)

Allopurinol is taken indefinitely.

Patients with the HLA-B*5801 allele have an increased risk of hypersensitivity to allopurinol

You should screen in Asian patients and black patients of African ancestry

It can cause serious adverse events like SJS/TLS, and DRESS.

Advise patients to look for skin changes

An excellent thread hot off the presses from kidney week on gout management in CKD!

https://twitter.com/NephroSeeker/status/1720859874383241512?s=20

A short and sweet summary of gout!

https://twitter.com/DrAmirKhanGP/status/1635332864874250240?s=20

If you remember nothing else:

- Gout flares are caused by more than increases in UA!

- Don't miss a septic joint

- Tap the joint if diagnosis uncertain - always send cultures

- Treat with early NSAIDs or colchicine

- Continue allopurinol during flares

- Goal UA <6

For making it this far, here's the checklist, differential, and sample EHR dotphrase for admitting a patient with an acute gout flare.

You can also find the downloadable PDF on the @pointofcaremed website.

You can read the unrolled version of this thread here: https://typefully.com/ROKeefeMD/d9NhmsN

Acute Gout Flare 201

Here are some of the highest-yield pearls related to the treatment of CAP!

Let me know what your favorite pearls are, and if you'd add anything!

- Thread -

Atypical bacteria need to be treated with something other than a beta-lactam because they either have absent or unique cell walls.

Azithromycin or doxycycline both inhibit bacterial protein synthesis.

Doxy can cause pill esophagits and sun-sensitivity.

Fluoroquinolones (but not so much azithromycin!) can prolong QT, be wary if on other prolonging meds.

Need to highlight this great @emcrit article!

https://emcrit.org/pulmcrit/myth-busting-azithromycin-does-not-cause-torsade-de-pointes-or-increase-mortality/

Ciprofloxacin is less effective than levofloxacin or moxifloxacin at treating pneumococcal respiratory infections and should be avoided in pneumonia.

The reason is that it has less gram-positive coverage (need to cover for strep pneumo!) and less lung penetration.

HFNC can help reduce work of breathing and stave off intubation in severe CAP.

It may be better than BIPAP since patients can tolerate it for longer and it allows for easier clearance of secretions.

In general, unless you are concerned about poor source control, resistance, or new infection, 7 days of antibiotics is likely sufficient to treat pneumonia even in severe CAP and in sick ICU patients with MRSA or pseudomonas.

Only give metronidazole or clindamycin if you are concerned about lung abscess or empyema because these represent non-oxygenated areas in or around the lung where anaerobes can grow.

Do not add anaerobic coverage for run of the mill aspiration pneumonia.

When covering for MRSA,

Daptomycin cannot be used for pneumonia since it is inactivated by surfactant

Linezolid can cause serotonin syndrome when given with other medications such as SSRIs and methadone

Parapneumonic effusions develop in the pleural space adjacent to a pneumonia.

They are seen in 20-57% of inpatients with pneumonia and 5-10% progress to empyema.

An empyema is purulence in the pleural space – these will always require drainage

It usually takes ~300cc of fluid for an effusion to be seen on CXR.

Effusions are “complicated” if the fluid has a positive gram stain (GS) or culture, or if the effusion is loculated.

In general, pleural effusions alone are rarely the cause of dyspnea or hypoxia unless it takes up > half of a hemithorax. If this is not the case, you should be thinking about other etiologies for a patient's symptoms.

If an effusion is large or loculated you will likely need to drain it via thoracentesis. Empyema may need a pigtail catheter to continuously drain.

If the patient does not improve with antibiotics or they keep getting recurrent pneumonia - think recurrent aspiration, underlying lung disease (COPD, bronchiectasis), post-obstructive (malignancy), immunodeficiency, or COP.

A CT may help clarify.

High-Yield Pearls for CAP Treatment

Here are some of the highest-yield pearls related to the clinical presentation and diagnosis of community-acquired pneumonia (CAP)!

Let me know what your favorite pearls are, and if you'd add anything!

- Thread -

You can still have a viral infection AND a bacterial pneumonia; having a positive RVP does not mean you should withhold antibiotics in the right clinical scenario!

CURB-65 and PSI are used to calculate mortality risk and have technically not been validated for determining the ideal place of care.

They can be valuable for helping you determine sick vs not sick, but in the end your clinical gut trumps all.

Rhinorrhea and sore throat are more commonly seen in URI and are less typical for CAP.

Sputum samples are usually not sent due to low sensitivity/yield.

Strep pneumo and H Flu are tough to grow in culture.

It is considered adequate if there are >25 PMNs and <10 squamous epithelial cells.

Otherwise, there is concern that the sample is saliva.

Note that this is NOT the same for tracheal aspirates in intubated ICU patients which can be VERY helpful for diagnosing a healthcare-associated pneumonia and identifying the bug and resistance patterns.

Only send blood cultures if there is concern for severe pneumonia or sepsis; they are positive in <20% of inpatients with PNA.

MRSA Nasal Swab has a 98% NPV for MRSA pneumonia.

Thus, in most cases, if it's negative, you can feel comfortable pulling off MRSA coverage

Note that this was only studied on the admission MRSA swab, not if the patient developed concern for HAP after being admitted.

Procalcitonin was validated in ICU settings to try and limit the duration of antibiotics. Thus, a procal on admission can be tough to interpret.

You can consider stopping abx if the level trends down to <80% of peak or is <0.25-0.50; note that it has variable sensitivity

If a patient's procalcitonin level is less than 0.5, it might be okay to stop giving them beta-lactam antibiotics but keep giving them azithromycin or doxycycline.

This is because gram negatives raise procalcitonin, whereas atypicals are less likely to raise it.

Legionella Urine Antigen should be sent in severe CAP, or there is concomitant hyponatremia, diarrhea, or recent exposure.

Note that the classic teaching of hyponatremia associated with legionella is likely overstated and not sensitive.

Bacterial pneumonia shouldn't cause pulmonary nodules. If present, it would be more consistent with a fungal infection in the right patient.

Beta-D-glucan (BDG) is sensitive but not specific for fungal infection.

Pearls for Diagnosing CAP

Pneumonia is the leading cause of infectious death in the US and one of the most common reasons for inpatient admission.

In IM, you'll see it over and over and over.

Here's my approach to the workup and management of inpatient CAP, along with some key pearls.

- Thread -

Check out these @pointofcaremed digital resources on CAP for use at the point of care!

They include admission checklists, HPI intakes, differentials, sample dotphrases for the EHR, and key clinical pearls, along with a podcast and YouTube video with accompanying slides.

First, what even is pneumonia (PNA)?

Simply put, it is inflammation of the lung parenchyma (most commonly caused by an infection) and can affect the alveoli, bronchioles, and interstitium.

The development of PNA is almost always associated with the microaspiration of either airborne pathogens or oropharyngeal secretions.

As such, PNA is often seen in patients with failure of lung-protective mechanisms like cough reflex and mucociliary clearance.

CAP is an infectious pneumonia contracted outside of a hospital setting.

Viruses are the most common cause of CAP.

The most common bacteria are Strep Pneumo, H. Flu, and Moraxella

However, a pathogen is only detected in 38% of patients admitted with concern for PNA.

When evaluating for bacterial CAP, focus on:

1. Evidence of systemic inflammation

- WBC with neutrophil predominance
- fever, chills, malaise

2. Pulmonary Symptoms

- hypoxia, productive cough, dyspnea
- less likely if sore throat or rhinorrhea

3. Opacities on CXR

Historically, some PNAs were noted to be "atypical" - they had milder symptoms, dry cough, interstitial pattern on CXR, and different response to antibiotics.

We now know this difference is because certain organisms preferentially exert their effect on the interstitium.

Confusingly, "atypical" can refer to either the PNA itself or bacteria that often cause it (i.e chlamydia, legionella, and mycoplasma).

Note, however, that "atypical" does not imply uncommon.

While "typical" lobar pneumonias are most commonly caused by strep pneumo, and "atypical" pneumonias by mycoplasma, a pathogen should not be assumed based on imaging alone.

Given that it is challenging to clinically distinguish between the two, the treatment is the same.

Pneumonia can cause hypoxia via infiltration and inflammation in the alveoli and interstitium, causing:

1. decreased ventilation and V/Q mismatch

2. intrapulmonary shunt (right to left) - blood continues to flow to affected areas and does not exchange oxygen

Here's a checklist I use when admitting a patient with suspected CAP.

Key Questions:

- Is this severe CAP requiring ICU?
- Is this actually a PE or ACS?
- Underlying pulmonary disease?
- Risk factors for MRSA or PsA?
- Prior infections or culture data?
- Value of a CT?

Severe CAP Criteria

Need for mechanical ventilation or pressor

OR

3 or more of:

- AMS
- Hypotension requiring resuscitation
- Hypothermia < 36 C
- RR > 30
- O2 requirement
- WBC < 4
- BUN > 20
- Plt < 100
- Multilobar PNA on CXR

CURB-65 and PSI are validated for predicting mortality, not necessarily the ideal site of care.

However, calculating these (along with assessing for severe CAP), can help you get a sense of sick vs not sick.

In the end, nothing trumps clinical judgment.

Here is the most pertinent info to collect for your HPI.

Key Questions:

- Systemic disease vs localized to lungs
- Trajectory of symptoms
- Exposures and unique risk factors

On exam, PNA may result in:

- reduced breath sounds
- bronchophony - increased clarity of voice
- egophany - E sounds like A
- tactile fremitus - vibrations more pronounced
- dullness to percussion

These are due to consolidation and increased density of lung tissue.

When thinking through your differential, its important to consider not only infectious etiologies, but also pneumonia mimics.

Don't miss:

- Severe PNA or sepsis
- MRSA or Pseudomonas
- PE
- ACS
- ADHF

Aspiration pneumonitis is aspiration of aggrevating substances into the airway without infection.

The imaging findings and symptoms are caused by lung parenchyma inflammation - its usually more abrupt, low-grade fever, and classically RML/RLL if upright vs RUL if supine

It's often tough to tell the difference between aspiration PNA and pneumonitis.

Most end up treating for CAP for 48 hours and stopping with rapid racovery.

If the CXR clears quickly, it was likely pneumonitis. CXR findings from pneumonia usually take months to clear.

Cryptogenic Organizing Pneumonia (COP) is a pneumonia-like disease and imaging appearance due to non-infectious chronic inflammation.

Be suspicious in repeat cases of PNAs seemingly unresponsive to abx.

Specifically lookout for a history of RA or amiodarone use.

Here's a sample plan for CAP.

The most important parts:

- Prompt initiation of abx to at least cover for typical and atypical organisms - commonly ceftriaxone and azithromycin

- Source control as needed

- CT if severe or unclear etiology

Urine legionella and pneumoccocal antigens are usually sent if severe CAP or in cases of a known outbreak.

Similarly, BCx are usually only sent in severe CAP or sepsis

Induced sputum cultures are rarely helpful unless you are concerned about resistance

If available, procalcitonin can be sent on admission and at 48 hours to assess trajectory and in cases where you have lower suspicion for bacterial PNA and want to pull off abx sooner.

In general, procal <0.5 makes a bacterial infection less likely.

https://twitter.com/ROKeefeMD/status/1700177205165543816

Per the CAPE COD trial (lol), patients admitted to the ICU with severe CAP should receive hydrocortisone 200mg daily for 4-7 days based on improved 28-day mortality (6.2% vs. 11.9%).

These patients likely overlap with sepsis patients who also benefit from steroids.

If you remember nothing else,

- Assess for severe CAP
- Viral etiologies are most common
- Its often tough to differentiate between "typical" vs "atypical" pneumonia pathogens
- Start prompt antibiotics if c/f bacterial PNA
- Discharge when afebrile and ~baseline

There are so many amazing reviews, trials, and other educational resources to learn more about CAP and that helped inform this thread. Here are just a few highlights!

The @PyrlsApp CAP Management Algorithm is particularly excellent! A great resource that I'm using more and more.

https://twitter.com/PyrlsApp/status/1635947748359905280

For making it this far, here's the checklist, differential, and sample EHR dotphrase for admitting a patient with CAP.

You can also find the downloadable PDF on the @pointofcaremed website.

You can read the unrolled version of this thread here: https://typefully.com/ROKeefeMD/3e8GaTs

Approach to Inpatient CAP: Workup and Management

As a senior resident, I thought I had a pretty strong understanding of sepsis and septic shock.

But after doing a deep dive, I realized there's so much nuance.

Here's my approach to workup and management, along with some key pearls and lessons.

- Thread -

Check out the @pointofcaremed digital resources on sepsis and septic shock for use at the point of care!

They include templates with admission checklists, sample dotphrases for the EHR, and key clinical pearls, along with a podcast and YouTube video with slides.

First of all, how do we even know if someone has sepsis?

Some history:

In 1991, SIRS criteria were established to identify those at high risk of sepsis-related death.

- HR >90
- RR >20
- WBC >12  or <4
- T >100.4 or <96.8

Sepsis was defined as 2/4 SIRS + e/o infection

However, the broad nature of SIRS commonly leads to misclassification.

For example, if I were to walk up a flight of stairs with my team on rounds, I very well might meet 2/4 SIRS criteria!

SIRS is sensitive but not specific.

In 2001, Sepsis-2 expanded and clarified the definitions but did not completely overhaul the system.

Sepsis was still SIRS + infection

Severe sepsis was sepsis with organ dysfunction

Septic shock was severe sepsis with hypotension unresponsive to fluids.

Between 2014-2016, Sepsis-3 got rid of "SIRS" and "severe sepsis" and made new definitions.

Sepsis:

"Life-threatening organ dysfunction caused by a dysregulated host response to infection"

Septic Shock:

"Sepsis PLUS pressor need and lactate >2 without hypovolemia"

Based on these, the SOFA score was introduced to focus on organ dysfunction.

However, SOFA is a bit cumbersome for use at the point of care (just look it up), so qSOFA was suggested as a more specific criterion for sepsis.

- RR >22
- systolic BP <100
- AMS

The pathophys of sepsis put VERY simply is an immune response to a pathogen leading to:

- vessel dilation + capillary leak
- microvascular thrombosis
- tissue ischemia
- acidosis

All resulting in organ dysfunction, often presenting as hypotension and respiratory distress.

Note that the core problem in sepsis is NOT hypovolemia, but rather vasodilation and poor perfusion.

Thus, aggressive fluid is not going to fix everything, and may in fact cause harm.

Be wary of just reacting to high lactate and low UOP - there are many reasons for each.

This in mind, here's a checklist when admitting a patient with suspected sepsis.

Key questions:

- Need for pressor?
- Need intubation?
- High risk of overload or pulm edema?
- Source?
- Source control?
- Prior culture data?

Here's a sample plan for sepsis.

The most important parts:

- 2x peripheral BCx + any indwelling line

- UA/UCx, CXR, lactate

- Broad-spectrum antibiotics

- Fluid to achieve euvolemia

- Pressor and steroid if persistently hypotensive

- Address severe acidosis

Antibiotics will almost always start broad with vancomycin and a beta-lactam (commonly cefepime or pip-tazo).

However, maintain a broad differential necessitating different tx, including:

- Atypical PNA
- C Diff
- Toxic shock or nec fasc
- Anaplasmosis
- Fungal
- Mimics

Some extra considerations for workup:

- Procalcitonin if equivocal
- Fungal markers if immunocompromised
- CT pan-scan if source unknown - consider source control

Trend:

- Daily CBC, CMP, coags
- Urine output via strict I/O's
- MAP
- Capillary refill, goal < 3 seconds

Some other pearls on workup and monitoring:

- PNA is the most common cause of sepsis

- Look out for ARDS, cholestasis, AKI, hepatic dysfunction, and DIC

- Good UOP is reassuring, but low UOP is nonspecific

Lactate is most commonly attributed to hypoperfusion and is viewed as something to be corrected.

However, it can instead be thought of as a reflection of endogenous epinephrine production.

Still, persistent elevation should draw extra attention to your management.

DDx for lactatemia:

Type A (tissue hypoxia)
- hypovolemia
- shock
- local ischemia (mesenteric, limb)
- decreased oxygenation
- anemia

Type B
- increased adrenergic state (albuterol, cocaine, epinephrine)
- decreased krebs (thiamine deficiency, EtOH)
- liver dysfunction

Procalcitonin is a measure of inflammation sensitive to bacteria, notably gram-negatives.

Though it's validated for ruling out HAP to discontinue abx in the ICU setting, if < 0.5, it's reasonable to say the etiology is less likely to be sepsis 2/2 a bacterial source.

Some pearls on fluid resuscitation:

- focus on euvolemia, MAP, and cap refill

- a good deal of fluid will leak out of vessels - much more than 2-3L (30cc/kg) of LR is rarely helpful

- low UOP or AKI may not be prerenal but rather ATN and will not improve with fluid

When it comes to pressors, many are taught:

norepi -> vaso -> epi

This often works well, but

- Norepi can lead to arrhythmias

- Vaso can be used first, but can't be given peripherally

- Epi is good in reduced EF or low HR

- Phenylephrine is ideal in AFib or AS

Here's a table for use at the point of care with some high-yield information for the commonly used vasopressors in sepsis.

MAP is the most reliable parameter for assessing response to therapy.

The goal is commonly MAP >65

The primary concern with low MAP is renal and cerebral injury.

In certain cases (i.e. dialysis), it may be okay to lower this goal and lower pressor needs.

Acidosis can worsen hypotension and respiratory distress via:

- Myocardial depression
- Decreased pressor efficacy
- Inceased arrythmia risk
- Compensatory increased RR

If pH < 7.1, consider bicarbonate

Just note that bicarb turns to pCO2 and must be ventilated off

The use of steroids in sepsis is a topic of debate.

Sepsis may lead to "relative adrenal insufficiency".

In general, if shock is refractory to low-med dose pressor, it's likely worth starting hydrocort 50mg q6.

Fludrocort is unlikely to add additional benefit.

Here's an approach to the daily presentation for patients with sepsis or septic shock I learned while in the ICU.

It helps you to keep track of all the moving parts while remaining thorough with your assessment and plan.

Here are some trials related to the management of sepsis and septic shock.

SMART - LR > NS in critically ill patients

SOAP II - dopamine increases risk of arrythmia vs norepi

CORTICUS Trial - hydrocort speeds up reversal of shock but does not reduce mortality

If you remember nothing else:

- Obtain cultures and promptly start antibiotics

- Source control

- Fluids are important but don't overdo it

- Don't delay starting pressor if MAP is < 65

- Watch MAP and cap refill, be cautious of responding only to UOP and lactate


For making it this far, here's a downloadable PDF with the checklist, differential, and sample EHR dotphrase for admitting a patient with sepsis and septic shock!


You can read the unrolled version of this thread here: https://typefully.com/ROKeefeMD/M8Z2vRO

Sepsis and Septic Shock

When I was an intern, I didn't even know what GDMT stood for.

It was challenging for me to keep track of all of the heart failure medications.

There weren't any great resources to help me remember the key medications.

So I made one.

Let's go through them.

- Thread -

Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) targets the pathophysiological mechanisms that contribute to heart failure progression.

Check out the @pointofcaremed podcast on GDMT!

https://spotifyanchor-web.app.link/e/kmnT8mKbSAb

Goals of GDMT in HFrEF:

- improve survival
- reduce hospitalizations
- improve symptoms

GDMT achieves this by:

- reducing oxygen demand and wall stress
- decreasing heart rate and contractility of the heart
- reducing the resistance that the heart needs to pump against

Some key terminology:

Preload - the volume of blood that is returned to the heart and present at the end of filling.

Afterload - the resistance the heart must overcome to eject blood during systole.