UMEM Educational Pearls

Drug-Drug Interactions in the Critically Ill

• Critically Ill ED patients are at risk for drug-drug interactions (DDIs) due to altered organ function, polypharmacy, and altered drug kinetics.
• DDIs involving the cytochrome isoenzyme CYP3A4 are of particular importance.
• CYP3A4 inhibitors, such as macrolides and azoles (fluconazole, voriconazole), can cause serious DDIs when given concomitantly with meds that are a subtrate for CYP3A4 - midazolam, cyclosporine, tacrolimus, diltiazem, amiodarone.
• Pay particular attention to your transplant patients, as administration of an azole can result in significant cyclosporine or tacrolimus toxicity.

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Pneumoperitoneum on CXR and CT

Pneumoperitoneum may be seen on an upright CXR up to 7 days after laparoscopic abdominal surgery/laparotomy and may be seen on abdominal CT for as long as three weeks after surgery. 

Elderly patients are at higher risk for skin infections for numerous reasons:
1. Blunted immune system response of skin to infections.
2. Slower wound repair after 3rd decade.
3. More frequent exposure to infections, especially drug resistant infections, especially if the patient is frequently hospitalized or in nursing homes.
4. Frequent portals of entry for skin infections: indwelling tubes and lines, leg ulcers, fissures and maceration on feet and between toes.

A key takeaway point is to always check the skin thoroughly of your elderly patients when searching for infections, especially the feet and toes!

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• Spondylolysis is a unilateral or bilateral defect in the pars interarticularis portion of the vertebrae.
• It is a stress fracture mostly seen in the lumbar vertebrae, and most commonly L5.
• Pain is relieved with rest and worsened by lateral bending or extension (NOTE: most back pain is worsened by flexion).
• If neurologic symptoms and/or radiculopathy are present, an alternative diagnosis should be considered, because they are rarely associated with spondylolysis.
• Diagnostic imaging should start with plain radiographs with added oblique views.
• Classically, oblique views show the Scotty dog sign with a crack on the dog’s neck/collar, the pars.

http://www.gentili.net/signs/images/400/spinescottyparsdefectdrawing.JPG

The Scotty dog’s head (superior articular facet), nose (transverse process), eye (pedicle), neck (pars interarticularis), and body (lamina) should be easily identified on the oblique radiograph.
 

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In a patient with toxin-induced bradycardia and hypotension, here is a quick differential to help identify the responsible substance:

• Beta blockers
• Calcium channel blockers
• Cholinergics
• Clonidine (and other alpha-2 agonists)
• Digoxin (and other cardiac glycosides)
• Opioids
• Sedative hypnotics (such as benzodiazepines and barbiturates)

Less commonly seen causes include: magnesium, propafenone, and plant toxins (aconitine, andromedotoxin, veratrine).

• The ability to detect brain CT abnormalities suggestive of ischemic stroke largely depends upon the time between the onset of symptoms and the CT examination.

• Large, cortical strokes are typically not detected on CT for at least 3 hours; Nearly 60% of strokes, however, are detectable on CT within 24 hours from time of infarct, and essentially 100% within 7 days.

• Clinical correlation:  Be sure that the reported time of symptom onset properly correlates with brain CT findings, as this could affect the decision to treat with tPA in accordance with appropriate time windows.  If a patient reports 1 hour of stroke symptoms, for example, and the brain CT shows significant edema and loss of gray/white matter differentiation suggesting infarct, be wary of a time discrepancy.

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Asthma, Peak Pressures, and the Ventilator

• In previous pearls, we have highlighted ventilator settings for the asthmatic, along with the differences between peak and plateau pressure measurements.
• When ventilating the asthmatic, pay attention to the ventilator settings placed by your respiratory therapist.
• In general, the respiratory therapist will set the ventilator to stop delivering tidal volumes when the peak pressure exceeds 40-60 cm H₂O.
• For asthmatics, this practice can result in very low tidal volumes.
• Thus, peak pressure limits must be set higher.
• As you know, high peak pressures have not been shown to be injurious, provided that the plateau pressure remains < 30 cm H₂O

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Risk Stratification in Pulmonary Embolism

The following are the principal markers useful for risk stratification:

• Clinical markers (shock, hypotension)
• Markers of RV dysfunction (RV dilatation, hypokinesis or pressure overload on echo, RV dilatation on CT, BNP elevation)
• Markers of myocardial injury (elevated troponin)

Patients with one or more of these markers have a higher mortality rate.

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The majority of "classic" symptoms and signs in elderly patients with pneumonia (fever, cough, sputum production, leukocytosis,chest pain) are unreliably present. However, tachypnea is one of the most reliable early findings in elderly patients with pneumonia, and in fact the same can be said about other serious bacterial illnesses in the elderly. The takeaway point here is simple: always count the respiratory rate in elderly patients (and don't trust those triage respiratory rates)!

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Diverticular Bleeding

• Diverticular bleeding is the  most common source of lower GI bleeds and accounts for 17 to 40 percent of cases
• The most common presentation (80%) is massive painless rectal bleeding. 
• Patients may have some cramping prior to a bloody bowel movement but otherwise will typically have no abdominal pain.
• The majority of the cases will resolve spontaneously, but those requiring more than 4 units of Packed Red Blood Cells should be considered for an angiogram or  surgery.
• Angiography can be used to localize the site of bleeding and embolize the bleeding source. 
• If embolization fails the patient may require a partial colectomy to treat the bleeding source.

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• About 15% of strokes are preceded by TIA.
• Within 90 days after a TIA, 10.5% will suffer a stroke.
• Of these, 21% will be fatal, 64% will be disabling, and half will occur within 1 to 2 days of the patient's emergency department visit.

Pre-existing acidosis and mechanical ventilation

• Not surprisingly, many critically ill ED patients often develop a metabolic acidosis.
• To compensate, patients hyperventilate, thereby producing a respiratory alkalosis.
• When these patients require intubation and mechanical ventilation, be sure to provide the same level of respiratory compensation when setting the ventilator. 
• Failing to provide a rate sufficient to compensate for the pre-intubation acidosis leads to a rapid drop in pH, bradycardia and eventually asystole.
• In general, rates can be increased to about 30-35 breaths per minute, after which auto-PEEP becomes problematic.

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Silent Pulmonary Embolism?

As many as 50% of patients with isolated DVT will be found to have silent pulmonary embolism (i.e. no chest pain or shortness of breath) on VQ scanning. Studies performed in the last year or so with CT scanning show that this percentage is much higher.

The clinical take-home point is NOT to get a pulmonary CTA on suspected DVT patients but to remember that many patients can and do have PE in the absence of cardiopulmonary symptoms. Pretty frightening....

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The WBC count is not an accurate predictor of bacteremia in the elderly. 20-45% of elderly patients with proven bacteremia have a normal WBC on presentation.

[from Caterino JM, et al. Bacteremic elder emergency department patients: procalcitonin and white count. Acad Emerg Med 2004;11:393-396.]

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Odontoid Fractures:

There are three types of C2 odontoid fractures:

1. Type I is an oblique fracture through the upper part of the odontoid process. This fracture is normailly stable and can be treated with a hard cervical collar.
2. Type II is a fracture occurring at the base of the odontoid as it attaches to the body of C2.  These fractures can be treated surgically, or conservatively with hard collar or a halo brace
3. Type III fractures occurs when the fracture line extends through the body of the axis. These fractures are normally treated surgically with or without a halo brace.

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• autossomal dominant disorder most commonly in Scandinavian and British descent due to deficiency of HMB-synthetase
• most heterozygotes are asymptomatic unless some factor increases the production of pyrogens, usually medications
• common drugs include steroids, alcohol, low calorie diets, and drugs (barbituates, sulfonamide antibiiotics, grisefulvin, and synthetic estrogens (birth-control)
• attacks of abdominal pain lasting several hours is the most common symptom and may be secondary to ileus or distension, but tenderness on exam and fever are absent
• peripheral neuropathy and muscle weakness improves over days, but may take years to return to normal
• diagnose: gold standard test measures RBC HMB-synthetase, screening test of normal PBG (porphobilinogen) level in urine rules out the condition
• treatment: narcotics, IV glucose (300g/day), and IV heme (4g/day)
   

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In the state of Maryland, the most common venomous snake is the copperhead. Though not as dangerous as the rattlesnake, it can still cause loss of function of limb and mortality in the pediatric patient.

Treatment has involved the use of CroFab (Protherics, Atlanta). This ovine derived monovalent immunoglobolin is actually made against the following snakes:

• Eastern diamondback rattlesnake
• Western diamondback rattlesnake
• Mojave rattlsnake
• Cottonmouth (Water moccasin)

Though efficacy has been shown with these snakes, we are hoping for cross-reactivity when we treat copperheads. There are case series and case reports (1) that have shown anectdotal improvement. We are still awaiting a real randomized controlled trial - may never happen.

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• Multiple Sclerosis (MS) is a relapsing condition caused by the destruction of myelin sheaths.
• Ninety percent of MS-related lesions can be detected on T2 MRI images.
• These lesions are typically para-ventricular, sometimes ovoid in shape (referred to as "Dawson's Fingers"), and often located on medullary veins.

Acute renal failure occurs in 1-25% of critically ill patients, with an associated mortality of 28 - 90%. 

The RIFLE Criteria represent the first consensus definition of acute renal failure used to classify critically ill patients as to their kidney function.  Notably, we use the worst possible classification according to the criteria, which measures either serum creatinine, urine output or both. 

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• 1006221408_RIFLE.jpg.doc (103 Kb)

The nitrite test on urine dipstick is commonly used for diagnosis of UTI. However, the test is only reliable in those bacteria that convert nitrates to nitrites, which primarily includes enterobaceriaceae. However, elderly patients often develop UTIs with Staph saprophyticus, pseudomonas, and enterococcus, none of which produce positive nitrites on dipstick testing. The takeaway point here is very simply....don't assume you've excluded UTI (esp. in elderly populations) just because the nitrite test is negative.

reference: Anderson RS, Liang SY. Infections in the elderly. Critical Decisions in Emergency Medicine, April 2010.

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