Complications of Alcohol

Today in morning report we discussed a patient presenting with worsening peripheral edema and ascites. 

This patient has a known history of cirrhosis secondary to alcohol.

It is important when assessing patients to have a framework of the likely causes for why they are presenting today, as well as to consider all of the dangerous complications/consequences of their underlying condition that often plays a role in their presentation. This will also help to shape your history/ddx/communications of the case.

In a patient with cirrhosis, some issues to consider when assessing:

1. Encephalopathy, also remember, think about what has caused their encephalopathy
2. SBP (Spontaneous bacterial peritonitis)
3. GI bleeds, specifically variceal bleeds.
4. Hyponatremia and neurologic sequelae from that.

Back to this patient. When assessed, there was no neurologic symptoms, mental status was normal, no evidence of asterixis. There was no abdominal tenderness, no fevers/chills/sweats. Lastly there was no evidence of melena stools or hematemesis. 

Because of his change in clinical status, the question of SBP was raised, and so a diagnostic tap was performed. 

A word on SBP:

Changes in clinical status in a patient with cirrhosis essentially warrants a diagnostic tap to ensure that they have not developed SBP. remember that SBP is mono-microbial due to transient bacteremia returning and seeding the ascitic fluid. It is not as previously thought due to GI translocation (if it were, would see polymicrobial infections). 

When doing your diagnostic tap, keep the number 250 in your head, which is the cut off of neutrophils below which is sensitive to rule out SBP.

If SBP is suspected, empiric treatment is targeted and enteric organisms and is often a 3rd generation cephalosporin. Additionally, for the treatment of SBP we will use albumin (in the absence of any other contraindications). In 1999 a study in the NEJM looked at ~65 patients in each arm of either cefotaxime or cefotaxime + albumin. Rates of renal impairment, and mortality were approximately 30% in the cefotaxime only arm compared to 10% in the cefotaxime + albumin arm. This gives an ARR of 20% and so a NNT of 5!! Granted was a small study, and the patient population needs to be assessed for whether it applies to your patient. However, this is an oft cited trial to support the use of albumin in SBP.

Last word on the neurologic complications of alcohol:

Acutely and most commonly is the intoxicating effects that alcohol has.
More seriously in the acute setting think about alcohol withdrawal, delirium tremens, Wernicke's. Chronically peripheral neuropathy, midline cerebellar disease, and rarely the marchiafava-bignami syndrome which is disease of the corpus callosum. 


See the 1999 NEJM SBP Albumin trial here

The definition is in the name.

Morning report discussed a case of a patient who was initially admitted for mild volume overload that was treated appropriately in the standard fashion, but while in hospital, abnormalities were noted on the patient's laboratory investigations...

They included:

1. Rising creatinine

2. Rising phsophate

3. Dropping Calcium

4. Very elevated uric acid

Context helps, and the further information revealed that this patient has a history of a hematologic malignancy, that has been treated with aggressive, multi-modal chemotherapy, and unfortunately has recurred with signficant tumour burden.

Diagnosis......Tumour Lysis Syndrome.

Tumour Lysis Syndrome (TLS) is aptly named, and helps to understand the basic pathophys.

Tumour cells breakdown and release their intracellular contents, specifically K, UA, PO4, and as a result of the high PO4, binds and lowers Ca.

Thus there are laboratory criteria for TLS, essentially being:

1. Hyperkalemia

2. Hyperuricemia

3. Hyperphosphatemia

4. Hypocalcemia.

Clinical criteria, are essentially all the downstream problems that the above can cause, with the big categories being:

1. AKI (think about calcium, UA, possibly xanthine precipitation)

2. Cardiac (dysrhytmias from K and Ca abnormalities)

3. Neuro (tetany, seizures)

TLS also can lead to a general inflammatory "SIRS" like reaction that can contribute to multi-organ failure.

Risk Factors for TLS include

1. Type of cancer (usually hematologic, rapidly progressive, but now noticing in other cancers previously thought to be rare).

2. Tumour burden (ie mets, bulk).

3. Treatment factors: highly aggressive, rapid cell turnover treatment 

4. Patient factors: do they have underlying kidney disease, hypovolemia, etc.?

5. MD factors: did we prophylax, give fluids

Priniciples of management:

1. Fluids, fluids, fluids

2. Excretion: whether through agents such as rasburicase (that facilitate excretion by converting UA to allantoin. Remember that allopurinol only inhibits formation of more UA, but does not mediate excretion.

Diuretics can be used. Dialysis often considered in severe cases. 

See this 2011 review article from the NEJM for more details.

The diagnosis is stroke...

wait how old is the patient?

In morning report we discussed a patient who presented with a history of expressive aphasia and right sided weakness.

If this patient were 80 years old with atrial fibrillation not anticoagulated, or if they had multiple vascular risk factors, then it would be a common case of ischemic stroke that we encounter not infrequently.

How would your diagnostic consideration change if this patient were 20, 30 or 40 years old?

In other words, how do you approach stroke in the young?

Before we explore that, remember to be diligent with your neurologic history to clarify:
1. time course
2. characteristics
3. localization
4. associated symptoms (important, and should revolve around your DDx).

This patient had difficulty speaking, remember that when assessing for a language problem, try to distinguish if there is a deficient in comprehension, repetition, naming, or fluency. Language localizes to the left perisylvian region.

The time course was over a couple days with primarily language deficits and mild weakness (later confirmed on exam). There were no obvious assoicated symptoms that we will explore in detail later.

Physical examination should be meant to help confirm/disconfirm your working diagnosis that was made from your history. Remember that the neurologic exam starts with:

1. Mental status: Language is part of the mental status exam
then:
2. Cranial Nerves
3. Motor: not just power!
4. Reflexes
5. Sensory
6. Coordination

This patient's physical exam confirmed word-finding difficulties and mild right sided weakness with no other abnormalities found on exam.

Imaging revealed a left MCA territory infarct and this patient is currently being managed and worked up to determine the etiology of the stroke.

A word on neuro-imaging (I am not a radiologist by any means, but some useful tips...in a sense radiology for dummies 101):

CT findings for stroke include: loss of grey/white matter differentiation, ribboning, sulcal effacement, MCA sign.
When looking at an MRI for stroke, one approach is first look at the FLAIR sequence...a stroke is white. Then look at the DWI (look at the 2nd or 3rd sequence), stroke should still be white...lastly look at the ADC: stroke will be black.

This patient was young, and getting back to the diagnostic approach for "Stroke in the Young".

Remember to consider the causes you normally would and so looking for vascular disease, arrythmia (atrial fibrillation) is still part of the work up.

Other etiologies and clues:

1. Arterial:
- Consider dissection, especially if there is a history of trauma, or neck manipulation, and especially if you detect a Horner's.
- Arterial embolism can result  from hypercoaguable states (thrombophilias, PV, APLA) as well as from emboli from other sources such as endocarditis.
- Consider other arteriopathies such as moya-moya 

2. Venous
- Venous sinus thrombosis can occur, especially in the setting of risk factors such as high estrogen containing OCP, and consider in a young patient with stroke complaining of headache.

3. Cardiac
- as previously mentioned endocarditis (both infectious and non- ie Libman-Sacks endocarditis in SLE)
- Cardiac anomalies, ventricular or atrial thrombi, PFO (controversial)

4. Medications
- In particular think of illicit drug use, such as stimulants that may further put at risk for hypertension, dissection.

5. Thrombophilia
- Includes myeloproliferative disorders, I also think of sickle cell here (though perhaps not a true thrombophilia), PNH, APLA, hyperhomocysteine, as well as other causes that can be investigated. 

6. Infectious causes of stroke
- Discussed endocarditis
- Also VZV, TB, Nocardia, neurocysticercosis
- Rheumatic disease, or Chagas as cause for cardioembolism.

7. Rarer things
- Genetic disorders (MELAS, CADASIL), primary vasculitis less commonly present with stroke with exception of APLA.

The differential as can be seen needs to be expanded when a "young" patient has a stroke, history and physical will still guide you to effectively investigate and manage.

See this review article in the Lancet for details.