Vancomycin Dosing in the Critically Ill Obese Patient

• Obesity related changes to drug metabolism and distribution can significantly impact the critically ill obese patient.
• Many meds can either be underdosed or overdosed depending on which body weight (ideal vs. actual) is used.
• With the increased incidence of MRSA infections, vancomycin is often included in the initial antibiotic selection for most critically ill ED patients.
• Importantly, vancomycin is one of the most studied antibiotics in obese patients.
• Recent guidelines recommend that an initial vancomycin dose of 25-30 mg/kg actual body weight be considered for any critically ill patient, with subsequent dosing dependent upon renal function and trough levels.

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Isoproterenol is a non-selective beta-1 and beta-2 agonist. The beta-1 effect produces an increase in heart rate, and the beta-2 effect produces mild vasodilation. Two times to consider its use are the following:
1. For overdriving pacing in cases of intermittent torsades de pointes when magnesium is ineffective.
2. For intractable bradycardia, this is another option besides dopamine or epinephrine. Because of the vasodilation, isoproterenol might be preferred to these other drugs when the bradycardia is accompanied by severe hypertension or when vasoconstrictors are not desired.

The drug is not commonly used anymore but is effective in treating persistent bradycardia or for overdrive pacing in patients with intermittent torsades de pointes when magnesium is ineffective. Be wary, though, that the beta-2 effect produces vasodilation so there may be a mild reduction in blood pressure when the drug is used.

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Commotio Cordis

Emergency medicine & sports medicine physicians often cover sporting events where athletes are at risk of commotio cordis

• 2nd most common cause of sudden cardiac death in young athletes in the US (HCM #1)
• Young males between 4 and 18 years old are at greatest risk
• 50% of all cases occur during competitive sports (baseball #1)
• Nonpenetrating, blunt trauma to the chest resulting to cardiac arrhythmia and, often, sudden cardiac  death.
• Ventricular fibrillation (VF) is the most common arrhythmia.
• Thought to occur secondary to a precordial impact during an electrically vulnerable portion of ventricular repolarization (10-30 msec before the T-wave peak)
• Treatment:  Immediate chest compressions and early use of an automated external defibrillator (AED) ((effective in only 15% of cases))
• Survival is much improved if resuscitation administered within 3 minutes (25%) than after 3 minutes (3%)
• Differential diagnosis: other causes of sudden cardiac death including HCM, coronary artery anomalies, long QT syndrome, Brugada syndrome, WPW, CAD, myocarditis, arrhythmogenic right ventricular dysplasia

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• syndrome of hematuria at the END of urination
• evidenced by spotting of blood in underwear
• occurs only in boys
• may last up to a year or longer
• symptoms are usually intermittent and recurrent
• physical examination is normal
• renal ultrasound usually helps rule out structural anomalies, but will usually be normal
• self-limited, with no specific therapy other than reassurance
   

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When you think of an acid or base causing a burn, you usually think of the local damage but there is one particular acid that causes systemic illness. Hydrofluoric Acid, found in your local Home Depot in brick/stone cleaning products, can cause severe illness despite a small total body surface area burn and exposure. A recent case report came out that illustrates how deadly HF can be. The reason is that this acid enters the body and chelates cations like calcium and potassium. The abstract is below but essentially hypocalcemia, hypokalemia leading to asystole 16hrs after exposure all from a 3% TBSA Burn - very impressive.

Background. Although hydrofluoric (HF) acid burns may cause extensive tissue damage, severe systemic toxicity is not common after mild dermal exposure. Case. A 36-year-old worker suffered a first-degree burn of 3% of his total body surface area as a result of being splashed on the right thigh with 20% HF acid. Immediate irrigation and topical use of calcium gluconate gel prevented local injury. However, the patient developed hypocalcemia and hypomagnesemia, hypokalemia, bradycardia, and eventually had asystole at 16 h post-exposure, which were unusual findings. He was successfully resuscitated by administration of calcium, magnesium, and potassium. Conclusion. This report highlights a late risk of HF acid dermal exposure.

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• Ischemic strokes often present as lacunar infarcts, wherein flow along the deep penetrating vessels of the middle cerebral artery is compromised.
• These strokes typically present with either purely motor or purely sensory neurologic deficit, in an ipsilateral pattern, often striking parts of the basal ganglia.
• Lacunar infarcts may present in a mild manner and carry the best prognosis for recovery relative to other types of ischemic stroke.

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The incidence and prevalence of thrombocytopenia in the ICU is poorly defined however, it has been found to be an independent predictor of death in the critically-ill. Increased mortality does not appear to be related to bleeding complications. On the other hand, survivors of critical illness tend to recover platelet faster as compared to non-survivors. 

Thrombocytopenia in the critically-ill is a marker for systemic inflammation/infection although the exact mechanisms are unknown. Common risk factors associated with thrombocytopenia in the ICU population are:

Sepsis

Renal failure

High-illness severity

Organ dysfunction

Bottom line:  Thrombocytopenia in the critically-ill is associated with increased mortality. 

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The September 5 2006 issue of Circulation contained a guideline, based on collaboration between the American Heart Assn, the American College of Cardiology, and the European Society of Cardiology, indicating that procainamide was preferable to amiodarone for the treatment of stable monomorphic ventricular tachycardia.

The 2010 AHA Guidelines have now also listed procainamide as the preferred drug for stable monomorphic ventricular tachycardia, giving it a Class IIa ("probably helpful") rating vs. amiodarone which has a Class IIb ("possibly helpful") rating. [thanks to Dr. Mike Abraham for pointing this out]

Procainamide is also the safest drug for use in tachydysrhythmias when an accessory pathway (e.g. Wolff-Parkinson-White syndrome) is present.

The caveat is that neither procainamide nor amiodarone should be used in the presence of a prolonged QTc.

Acute care physicians should (re-)familiarize themselves with the use of procainamide, and emergency departments should maintain quick access to this drug to stay up-to-date with current national and international guidelines.

 

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Septic Arthritis

It is generally taught that if the synovial fluid white blood count (WBC) is less than 50,000 it is not septic, however, there is growing evidence that a clear delineation in the WBC between septic arthritis and inflammatory arthritis is not possible.  In fact, inflammatory arthritis (rheumatoid and gout) actually increases your risk for septic arthritis and the two can coexist.  Gram stains of the fluid  only show organisms in 50% of those with septic arthritis so you also can not rely on them either.  Inflammatory markers (CRP, ESR) can be elevated with inflammatory or septic arthritis so they too can not differentiate between the two.

In the end, because of the risk of permanent joint dysfunction, it is important to make the diagnosis on clinical grounds and treat empirically if you are unsure.  Err on the sound of treatment.  Serial joint aspirations to drain synovial fluid have the same outcomes as operative washout.

A recent article that discusses the concerns with making the diagnosis of septic arthritis is:

Mathews et al. Bacterial septic arthritis in adults. Lancet (2010) vol. 375 (9717) pp. 846-55

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The answer was fomepizole would be the treatment for life-threatening disulfiram reaction. Blocks Alcohol Dehydrogenase and ironically prevent metabolism of ethanol and prolong intoxication.

I forgot how many see the pearls and the response was overwhelming. That was great and cost a me a little more. There were two winners:

Katie Baugher, PGY-1

Ari Keslter

Please email me how to best send you the gift certificate.

There are medications, if taken with ethanol, will cause a disulfiram reaction. This reaction results from inhibition of aldehyde dehydrogenase, the enzyme in ethanol metabolism that breaks acetaldehyde to acetic acid. The increase in acetaldehyde results in nausea, vomiting, diarrhea, flushing, palpitations and orthostatic hypotension. So if you prescribe a patient with any of these medications you must make certain to tell them NOT to drink any ethanol - that includes cough/cold preparations that have ethanol:

Antibiotics: Metronidazole(Flagyl), Trimethoprim-sulfamethoxazole (Bactrim)

Sulfonylureas: Chlorpropamide and tolbutamide

These have possible reactions: griseofulvin, quinacrine, procarbazine, phentolamine, nitrofurantoin

Bonus Question: $10 Starbuck's Gift Card for  first person that emails me with the answer to this question

What treatment could you give to someone suffering from a life threatening disulfiram reaction that biochemically should cure him? 

• Lhermitte's phenomenon is a transient, sensory symptom which likens an electric shock that radiates down the spine or into the limbs.

• The sensation is triggered by neck flexion.  The frequency with which they occur varies and the slightest movement of the head or neck may trigger it.

• This phenomenon occurs most frequently with multiple sclerosis, but can also be seen with other lesions of the cervical cord, including tumors, disc herniation, post-radiation myelopathy, and following trauma.

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The Importance of Antibiotic Timing for Sepsis and Septic Shock

• Septic shock is perhaps the most common critical illness that emergency physicians manage.
• In several studies, delays in initiating antibiotics for patients with septic shock were the strongest predictor of mortality.
• Broad spectrum antibiotics should be administered ASAP (preferably within 60 minutes) to patients with septic shock. 
• Selection of antibiotics should be based on the presumed source, the antibiogram at your institution, and the patient's risk factors for resistant organisms.
   

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Diagnosing Subarachnoid Hemorrhage-6 Pitfalls

1. Subarachnoid hemorrhage (SAH) doesn't always present as the "worst ever" headache. Don't most of our patients say their headache is the worst headache anyway? Be suspicious of the diagnosis if your patient has acute onset of an unusual or atypical headache. Diagnoses starts with the history.

2. The neuro exam may be completely normal in some cases, especially early on.

3. The headache due to SAH may get better with analgesics. This is a huge pitfall. Don't rule this diagnosis out if analgesics help.

4. The CT scan may be negative. Enough said.

5. Be careful with interpretation of the CSF. We all want the number of red cells in tube 4 to be zero. Be careful with this. Although the rbcs may have dropped by 50% from tubes 1 to 4, the diagnosis hasn't been excluded unless the cells clear completely. Although there have been some case reports of SAH with rbcs < 100, this is pretty uncommon.

6. CT Angiography and/or MRI with FLAIR is not a substitute for the lumbar puncture.

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Cervical Radiculopathy

The most commonly affected level is C7 (31-81%), followed by C6 (19-25%), C8 (4-12%) and C5 (2-14%)

Anterior compression can selectively affect motor fibers

Posterior compression can selectively affect sensory fibers

         -More common due to posterior lateral disc herniation or facet degeneration

Signs and symptoms: Sensory complaints (findings are in a root distribution) and possible weakness and reflex changes.

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In the past several years it has become common practice to use cuffed tubes for pediatric intubations.  However, a recent study suggests that cuff pressures are not as well regulated in pediatric patients, particularly when the patients are quickly intubated prior to aeromedical transport. Cuff pressures >30 cm H2O are associated with tracheal damage, however, up to 41% of pediatric patients transferred had cuff pressures >30 cm H2O, and 30% of those had pressures >60 cm H2O!  

So:

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Most cases of normal anion gap metabolic acidosis result from either urinary (RTA) or gastrointestinal HCO₃^- losses (diarrhea).  A number of xenobiotics can also cause this disorder:

1. Acetazolamide
2. Acidifying Agents: Ammonium chloride, arginine hydrochloride, hydrochloric acid, lysine hydrochloride
3. Cholestyramine
4. Toluene
5. Topiramate (Topamax)

• Transverse Myelitis (TM) is the development of grey and white matter inflammation of the spinal cord, which can result in demyelination.
• Hallmark characteristics of this condition include: (1) isolated spinal cord (not brain) dysfunction, and (2) the lack of associated cord compression.
• TM can be acute or subacute, such that it progresses over the course of hours to several days.  Nearly half of cases will reach its maximal deficit within 1 to 10 days of onset.
• The diagnosis of TM is primarily based on the history and physical examination findings.  MRI of the spinal cord and myelography are often used as diagnostic adjuncts.
• This condition typically presents with paresthesias, back pain, and ascending leg weakness.
• Febrile illnesses often serve as a precursor; one series found this to be the case in 37% of complete TM cases.
• While steroids are sometimes administered over the first several days of illness to decrease inflammation, there is no cure for TM and treatment is largely supportive in nature. 

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Linezolid is used for gram-positive infections resistant to conventional therapy (e.g., Vancomycin-resistant enterococcus and Methicillin Resistant Staph Aureus). Linezolid is an oxazolidinone, but more importantly it is a weak monoamine oxidase inhibitor (MAOI) and serotonin syndrome (e.g., altered mental status, neuromuscular abnormalities, autonomic instability) may occur when combined with selective serotonin re-uptake inhibitors (SSRIs) or with recent discontinuation of SSRI. 

Be aware that the following drugs can precipitate serotonin syndrome when combined with Linezolid:

Mirtazpine       Buproprion       Fentanyl

Trazodone       Buspirone         Bromocryptine

Levodopa        Lithium               Amphetamines

Cocaine           Codeine            Reserpine

Ergots               MAOI's

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